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4. Effect of alirocumab on lipoprotein(a) and cardiovascular risk after acute coronary syndrome

Author

Bittner, V. A. (Vera A.), Szarek, M. (Michael), Aylward, P. E. (Philip E.), Bhatt, D. L. (Deepak L.), Diaz, R. (Rafael), Edelberg, J. M. (Jay M.), Fras, Z. (Zlatko), Goodman, S. G. (Shaun G.), Halvorsen, S. (Sigrun), Hanotin, C. (Corinne), Harrington, R. A. (Robert A.), Jukema, W. (Wouter), Loizeau, V. (Virginie), Moriarty, P. M. (Patrick M.), Moryusef, A. (Angèle), Pordy, R. (Robert), Roe, M. T. (Matthew T.), Sinnaeve, P. (Peter), Tsimikas, S. (Sotirios), Vogel, R. (Robert), White, H. D. (Harvey D.), Zahger, D. (Doron), Zeiher, A. M. (Andreas M.), Steg, G. (Gabriel), Schwartz, G. G. (Gregory G.), and Huikuri, H. (Heikki)

Subjects
low-density lipoprotein cholesterol, proprotein convertase subtilisin/kexin type 9 inhibition, lipids (amino acids, peptides, and proteins), acute coronary syndromes, alirocumab, cardiovascular diseases, major adverse cardiovascular events
Abstract

Background: Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C). Objectives: A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE). Methods: One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina. Results: Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081). Conclusions: Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)

Published
2020

5. Effects of Alirocumab on Cardiovascular Events After Coronary Bypass Surgery

Author

Szarek, M, Bhatt, DL, Bittner, VA, Diaz, R, Edelberg, JM, Hanotin, C, Harrington, RA, Jukema, JW, Letierce, A, Moryusef, A, Pordy, R, Lopez, GAR, Roe, MT, White, HD, Zeiher, AM, Steg, PG, Schwartz, GG, Aylward, PE, Drexel, H, Sinnaeve, P, Dilic, M, Goodman, SG, Prieto, JC, Yong, H, Lopez-Jaramillo, P, Pecin, I, Reiner, Z, Ostadal, P, Poulsen, SH, Viigimaa, M, Nieminen, MS, Danchin, N, Chumburidze, V, Tse, HF, Xavier, D, Zahger, D, Valgimigli, M, Kimura, T, Kim, HS, Kim, SH, Erglis, A, Laucevicius, A, Kedev, S, Yusoff, K, Alings, M, Halvorsen, S, Flores, RMC, Sy, RG, Budaj, A, Morais, J, Dorobantu, M, Karpov, Y, Ristic, AD, Chua, T, Murin, J, Fras, Z, Tunon, J, de Silva, HA, Muller, C, Ray, KK, Vogel, R, Chaitman, B, Kelsey, SF, Olsson, AG, Rouleau, JL, Simoons, ML, Alexander, K, Meloni, C, Rosenson, R, Sijbrands, EJG, Alexander, JH, Armaganijan, L, Bagai, A, Bahit, MC, Brennan, JM, Clifton, S, DeVore, AD, Deloatch, S, Dickey, S, Dombrowski, K, Ducrocq, G, Eapen, Z, Endsley, P, Eppinger, A, Hess, CN, Hlatky, MA, Jordan, JD, Knowles, JW, Kolls, BJ, Kong, DF, Leonardi, S, Lillis, L, Maron, DJ, Marcus, J, Mathews, R, Mehta, RH, Mentz, RJ, Moreira, HG, Patel, CB, Pereira, SB, Perkins, L, Povsic, TJ, Puymirat, E, Jones, WS, Shah, BR, Sherwood, MW, Stringfellow, K, Sujjavanich, D, Toma, M, Trotter, C, van Diepen, SFP, Wilson, MD, Yan, ATK, Schiavi, LB, Garrido, M, Alvarisqueta, AF, Sassone, SA, Bordonava, AP, De Lima, AEA, Schmidberg, JM, Duronto, EA, Caruso, OC, Novaretto, LP, Hominal, MA, Montana, OR, Caccavo, A, Vilamajo, OAG, Lorenzatti, AJ, Cartasegna, LR, Paterlini, GA, Mackinnon, IJ, Caime, GD, Amuchastegui, M, Codutti, OR, Jure, HO, Bono, JOE, Hrabar, AD, Vallejos, JA, Rodolfo, AAG, Novoa, F, Patocchi, CA, Zaidman, CJ, Giuliano, ME, Dran, RD, Vico, ML, Carnero, GS, Guzman, PN, Allende, JCM, Brasca, DFG, Labarta, MHB, Nani, S, Blumberg, EDS, Colombo, HR, Liberman, A, Luciardi, HL, Waisman, GD, Berli, MA, Duran, ROG, Cestari, HG, Luquez, HA, Giordano, JA, Saavedra, SS, Waites, JH, Collins, N, Soward, A, Hii, CLS, Shaw, J, Arstall, MA, Horowitz, J, Rogers, JF, Colquhoun, D, Flores, REO, Roberts-Thomson, P, Raffel, O, Lehman, SJ, Coverdale, SGM, Garrahy, PJ, Starmer, G, Sader, M, Carroll, PA, Zweiker, R, Hoppe, U, Huber, K, Berger, R, Weidinger, F, Faes, D, Hermans, K, Pirenne, B, Leone, A, Hoffer, E, Vrolix, MCM, De Wolf, L, Wollaert, B, Castadot, M, Dujardin, K, Beauloye, C, Vervoort, G, Striekwold, H, Convens, C, Roosen, J, Barbato, E, Claeys, M, Cools, F, Terzic, I, Barakovic, F, Midzic, Z, Pojskic, B, Fazlibegovic, E, Durak-Nalbantic, A, Vulic, D, Muslibegovic, A, Reis, G, Sousa, L, Nicolau, JC, Giorgeto, FE, Silva, RP, Maia, LN, Rech, R, Rossi, PRF, Cerqueira, MJAG, Duda, N, Kalil, R, Kormann, A, Abrantes, JAM, Pimentel, P, Soggia, AP, de Santos, MON, Neuenschwander, F, Bodanese, LC, Michalaros, YL, Eliaschewitz, FG, Vidotti, MH, Leaes, PE, Botelho, RV, Kaiser, S, Manenti, ERFF, Precoma, DB, Jorge, JCM, Silva, PGMD, Silveira, JA, Saporito, W, Marin, JA, Feitosa, GS, Ritt, LEF, de Souza, JA, Costa, F, Souza, WKSB, Reis, HJL, Lopes, RD, Machado, L, Ayoub, JCA, Todorov, GV, Nikolov, FP, Velcheva, ES, Tzekova, ML, Benov, HO, Petranov, SL, Tumbev, HS, Shehova-Yankova, NS, Markov, DT, Raev, DH, Mollov, MN, Kichukov, KN, Ilieva-Pandeva, KA, Gotcheva, NN, Ivanova, R, Mincheva, VM, Lazov, PV, Dimov, BI, Senaratne, M, Stone, J, Kornder, J, Pearce, S, Dion, D, Savard, D, Pesant, Y, Pandey, A, Robinson, S, Gosselin, G, Vizel, S, Hoag, G, Bourgeois, R, Morisset, A, Sabbah, E, Sussex, B, Kouz, S, MacDonald, P, Diaz, A, Michaud, N, Fell, D, Leung, R, Vuurmans, T, Lai, C, Nigro, F, Davies, R, Nogareda, G, Vijayaraghavan, R, Ducas, J, Lepage, S, Mehta, S, Cha, J, Dupuis, R, Fong, P, Rodes-Cabau, J, Fadlallah, H, Cleveland, D, Huynh, T, Bata, I, Hameed, A, Pincetti, C, Potthoff, S, Acevedo, M, Aguirre, A, Vejar, M, Yanez, M, Araneda, G, Fernandez, M, Perez, L, Varleta, P, Florenzano, F, Huidobro, L, Raffo, CA, Olivares, C, Chen, JY, Dong, YG, Huang, WJ, Wang, JZ, Huang, SA, Yao, ZH, Cui, L, Lin, WH, Sun, YM, Wang, JF, Li, JP, Zhang, XL, Zhu, H, Chen, DD, Huang, L, Dong, SH, Su, GH, Xu, B, Su, X, Cheng, XS, Lin, JX, Zong, WX, Li, HM, Feng, Y, Xu, DL, Yang, XC, Ke, YN, Lin, XF, Zhang, Z, Zheng, ZQ, Luo, ZR, Chen, YD, Ding, CH, Zheng, Y, Li, XD, Peng, DQ, Li, Y, Wei, M, Liu, SW, Yu, YH, Qu, BM, Jiang, WH, Zhou, YJ, Zhao, XS, Yuan, ZY, Guo, Y, Xu, XP, Shi, XB, Ge, JB, Fu, GS, Bai, F, Fang, WY, Shou, XL, Yang, XJ, Wang, JA, Jaramillo, N, Vallejo, GS, Botia, DCL, Lopez, RB, De Salazar, DIM, Bonfanti, AJC, Higuera, JD, Silva, SIB, Lozada, HJG, Arroyo, JAC, Mendoza, JLA, Ruiz, RLF, Fernandez, AM, Jatin, FGM, Herazo, AS, Parada, JC, Triana, MAU, Spinar, J, Horak, D, Stasek, J, Alan, D, Machova, V, Linhart, A, Novotny, V, Kaucak, V, Rokyta, R, Naplava, R, Coufal, Z, Adamkova, V, Podpera, I, Zizka, J, Motovska, Z, Marusincova, I, Svab, P, Heinc, P, Kuchar, J, Povolny, P, Raungaard, B, Clemmensen, P, Bang, LE, May, O, Bottcher, M, Hove, JD, Frost, L, Gislason, G, Larsen, J, Johansen, PB, Hald, F, Jeppesen, J, Nielsen, T, Kristensen, KS, Walichiewicz, PM, Lomholdt, JD, Klausen, IC, Nielsen, PK, Davidsen, F, Videbaek, L, Soots, M, Vahula, V, Hedman, A, Soopold, U, Martsin, K, Taskinen, MR, Porthan, K, Airaksinen, JK, Juonala, M, Kiviniemi, T, Vikman, S, Posio, P, Taurio, J, Huikuri, H, Kaikkonen, K, Coste, P, Ferrari, E, Morel, O, Montalescot, G, Barone-Rochette, G, Mansourati, J, Cottin, Y, Leclercq, F, Belhassane, A, Delarche, N, Boccara, F, Paganelli, F, Clerc, J, Schiele, F, Aboyans, V, Probst, V, Berland, J, Lefevre, T, Khintibidze, I, Shaburishvili, T, Pagava, Z, Ghlonti, R, Lominadze, Z, Khabeishvili, G, Hemetsberger, R, Rauch-Krohnert, U, Stratmann, M, Appel, KF, Schmidt, E, Omran, H, Stellbrink, C, Dorsel, T, Lianopoulos, E, Marx, R, Zirlik, A, Schellenberg, D, Heitzer, T, Laufs, U, Marx, N, Gielen, S, Winkelmann, B, Behrens, S, Sydow, K, Simonis, G, Muenzel, T, Werner, N, Leggewie, S, Bocker, D, Braun-Dullaeus, R, Toursarkissian, N, Jeserich, M, Weissbrodt, M, Schaeufele, T, Weil, J, Voller, H, Waltenberger, J, Natour, M, Steiner, S, Heidenreich, L, Gremmler, U, Killat, H, Patsilinakos, S, Kartalis, A, Manolis, A, Sionis, D, Liberopoulos, E, Skoumas, I, Athyros, V, Parthenakis, PIF, Hahalis, PIG, Lekakis, J, Xatzitolios, A, Ovando, SRF, Valdovinos, PCM, Benecke, JLA, De Leon, ERR, Yan, BPY, Siu, DCW, Turi, T, Merkely, B, Kiss, RG, Ungi, I, Lupkovics, G, Nagy, L, Katona, A, Edes, I, Muller, G, Horvath, I, Kapin, T, Falukozy, J, Kumbla, M, Sandhu, M, Annam, S, Proddutur, NR, Premchand, RK, Mahajan, A, Abhyanakar, AD, Kerkar, P, Govinda, RA, Oomman, A, Sinha, D, Patil, SN, Kahali, D, Sawhney, J, Joshi, AB, Chaudhary, S, Harkut, P, Guha, S, Porwal, S, Jujjuru, S, Pothineni, RB, Monteiro, MR, Khan, A, Iyengar, SS, Grewal, JS, Chopda, M, Fulwani, MC, Patange, A, Chopra, VK, Goyal, NK, Shinde, R, Manakshe, GV, Patki, N, Sethi, S, Munusamy, V, Karna, S, Adhyapak, S, Pandurangi, U, Mathur, R, Kalashetti, S, Bhagwat, A, Raghuraman, B, Yerra, SK, Bhansali, P, Borse, R, Das, S, Abdullakutty, J, Saathe, S, Palimkar, P, Atar, S, Shechter, M, Mosseri, M, Arbel, Y, Lotan, C, Rosenschein, U, Katz, A, Henkin, Y, Francis, A, Klutstein, M, Nikolsky, E, Turgeman, Y, Halabi, M, Kornowski, R, Jonas, M, Amir, O, Rozenman, Y, Fuchs, S, Hussein, O, Gavish, D, Vered, Z, Caraco, Y, Elias, M, Tov, N, Piovaccari, G, De Pellegrin, A, Guardigli, G, Licciardello, G, Auguadro, C, Cuccia, C, Salvioni, A, Musumeci, G, Calabro, P, Novo, S, Faggiano, P, De Cesare, NB, Berti, S, Cavallini, C, Puccioni, E, Galvani, M, Tespili, M, Piatti, P, Palvarini, M, De Luca, G, Violini, R, De Leo, A, Filardi, PP, Ferratini, M, Dai, K, Kamiya, H, Ando, K, Takeda, Y, Morino, Y, Hata, Y, Kimura, K, Kishi, K, Michishita, I, Uehara, H, Higashikata, T, Hirayama, A, Hirooka, K, Sakagami, S, Taguchi, S, Koike, A, Fujinaga, H, Koba, S, Kozuma, K, Kawasaki, T, Ono, Y, Shimizu, M, Katsuda, Y, Wada, A, Shinke, T, Ako, J, Fujii, K, Takahashi, T, Sakamoto, T, Furukawa, Y, Sugino, H, Mano, T, Utsu, N, Ito, K, Haraguchi, T, Ueda, Y, Nishibe, A, Fujimoto, K, Yoon, JH, Park, HS, Chae, IH, Kim, MH, Jeong, MH, Rha, S, Kim, C, Hong, T, Busmane, A, Pontaga, N, Strelnieks, A, Mintale, I, Sime, I, Petrulioniene, Z, Kavaliauskiene, R, Jurgaitiene, R, Sakalyte, G, Slapikas, R, Norkiene, S, Misonis, N, Kibarskis, A, Kubilius, R, Bojovski, S, Lozance, N, Kjovkaroski, A, Doncovska, S, Ong, TK, Kasim, S, Maskon, O, Kandasamy, B, Liew, HB, Mohamed, WMIW, Castillo, AG, Calvillo, JC, Campos, PF, Fragoso, JCN, Llamas, EAB, Gamba, MAA, Madrigal, JC, Salas, LGG, Rosas, EL, Diaz, BG, Vazquez, ES, Ackar, AN, Esperon, GAL, Sanchez, CRM, De Leon, MG, Otero, RS, Salmon, GF, Rios, JAP, Ruiz, JAG, Breedveld, RW, Hoogslag, PAM, Suryapranata, H, Oomen, A, Wiersma, JJ, Van Der Wal, RMA, Van Huysduynen-Monraats, PSH, Karalis, I, Verdel, GJE, Brueren, BRG, Troquay, RPT, Viergever, EP, Al-Windy, NYY, Bartels, GL, Cornel, JH, Hermans, WRM, Herrman, JPR, Bos, RJ, Groutars, RGEJ, Van Der Zwaan, CC, Kaplan, R, Ronner, E, Groenemeijer, BE, Bronzwaer, PNA, Liem, AAH, Rensing, BJWM, Bokern, MJJA, Nijmeijer, R, Hersbach, FMRJ, Willems, FF, Gosselink, ATM, Elliott, J, Wilkins, G, Fisher, R, Scott, D, Hart, H, Stewart, R, Harding, S, Ternouth, I, Fisher, N, Aitken, D, Anscombe, R, Tomala, T, Nygard, O, Sparby, JA, Andersen, K, Gullestad, L, Jortveit, J, Munk, PS, Hurtig, U, Ticona, JRC, Velasquez, JRD, Miguel, SAN, Perez, ESS, Chambilla, JMC, Ayala, CAC, Leon, RPC, Gonzales, RJV, Zuniga, JDH, Cosavalente, LAC, Mannucci, JEB, Navarro, NCL, Concha, YMR, Chavez, VER, Hernandez, HAA, Nunez, CAZ, Ferrolino, A, Sy, RAG, Tirador, L, Matiga, G, Coching, RM, Bernan, A, Rogelio, G, Morales, DD, Tan, E, Wlodarczak, A, Jaworska, K, Skonieczny, G, Pawlowicz, L, Wojewoda, P, Busz-Papiez, B, Bednarski, J, Goch, A, Staneta, P, Dulak, E, Saminski, K, Krasowski, W, Sudnik, W, Zurakowski, A, Skorski, M, Lysek, R, Miklaszewicz, B, Kubica, J, Lipko, JA, Kostarska-Srokosz, E, Piepiorka, M, Drzewiecka, A, Sciborski, R, Stasiewski, A, Blicharski, T, Bystryk, L, Szpajer, M, Korol, M, Czerski, T, Mirek-Bryniarska, E, Gniot, J, Lubinski, A, Gorny, J, Franek, E, Monteiro, P, Bastos, JM, Pereira, HH, Martins, D, Seixo, F, Mendonca, C, Botelho, A, Minescu, B, Istratoaie, O, Tesloianu, DN, Cristian, G, Podoleanu, CGC, Constantinescu, MCA, Bengus, CM, Militaru, C, Rosu, D, Parepa, IR, Matei, AV, Alexandru, TM, Shvarts, Y, Orlikova, O, Kobalava, Z, Barbarash, OL, Markov, V, Lyamina, N, Gordienko, A, Zrazhevsky, K, Vishnevsky, AY, Gurevich, V, Stryuk, R, Lomakin, NV, Bokarev, I, Shalaev, S, Khaisheva, L, Chizhov, P, Viktorova, I, Osokina, N, Akatova, E, Chumakova, G, Libov, I, Voevoda, MI, Tretyakova, TV, Baranov, E, Shustov, S, Yakushin, S, Gordeev, I, Khasanov, N, Reshetko, O, Sotnikova, T, Molchanova, O, Nikolaev, K, Gapon, L, Baranova, E, Shogenov, Z, Kosmachova, E, Povzun, A, Egorova, L, Tyrenko, VV, Ivanov, IG, Simic, D, Ivanovic, N, Davidovic, G, Tasic, N, Asanin, MR, Stojic, S, Apostolovic, SR, Ilic, S, Putnikovic, B, Stankovic, A, Arandjelovic, A, Radovanovic, S, Balinovac, J, Dincic, DV, Seferovic, P, Dodic, S, Dimkovic, S, Poh, KK, Ong, HY, Micko, K, Nociar, J, Pella, D, Fulop, P, Hranai, M, Palka, J, Mazur, J, Majercak, I, Dzupina, A, Fazekas, F, Gonsorcik, J, Bugan, V, Selecky, J, Kamensky, G, Strbova, J, Smik, R, Dukat, A, Zuran, I, Oklukar, J, Suligoj, NC, Cevc, M, Lipar, L, Cyster, HP, Ranjith, N, Corbett, C, Bayat, J, Makotoko, EM, Kapp, IE, Basson, MMD, Lottering, H, Van Zyl, LJ, Sebastian, PJ, Pillay, T, Saaiman, JA, Commerford, PJ, Cassimjee, S, Ebrahim, IO, Sarvan, M, Mynhardt, JH, Dalby, AJ, Reuter, H, Moodley, R, Vida, M, Fillat, ARC, Peris, VB, Jimenez, FF, Marin, F, Fernandez, JMC, Gil-Extremera, B, Diz, FW, Garcia-Dorado, D, Iniguez, A, Fernandez, JT, Gonzalez-Juanatey, JR, Portales, JF, Murillo, FC, Pericas, LM, Zamorano, JL, Martin, MD, Cortada, JB, Martin, JJA, Fernandez, JRD, Fernandez, JFD, Lledo, JAG, Sales, JC, Rodriguez, JB, Tragant, GG, Benedicto, A, Gonzalez-Juanatey, C, Potau, MC, Perez, IP, De La Tassa, CM, Rincon, PLO, Recena, JB, Escudier, JM, Constantine, G, Haniffa, R, Tissera, N, Amarasekera, S, Fernando, N, Jayawardena, J, Santharaj, W, Ekanayaka, R, Mendis, S, Senaratne, V, Mayurathan, G, Sirisena, T, Rajapaksha, A, Herath, JI, Amarasena, N, Berglund, S, Rasmanis, G, Hagstrom, E, Witt, N, Mourtzinis, G, Nicol, P, Hansen, O, Romeo, S, Torstensson, I, Jensen, SA, Ahremark, U, Sundelin, T, Moccetti, T, Mach, F, Binder, R, Chiang, CE, Tsai, WC, Ueng, KC, Lai, WT, Liu, ME, Hwang, JJ, Yin, WH, Hsieh, IC, Kuo, JY, Huang, TY, Fang, CY, Kaewsuwanna, P, Soonfuang, W, Jintapakorn, W, Sukonthasarn, A, Sritara, P, Wongpraparut, N, Sastravaha, K, Sansanayudh, N, Kehasukcharoen, W, Piyayotai, D, Camsari, A, Kultursay, H, Guneri, S, Mutlu, B, Ersanli, M, Demirtas, M, Kirma, C, Ural, E, Koldas, L, Karpenko, O, Prokhorov, A, Vakaluyk, I, Myshanych, H, Reshotko, D, Batushkin, V, Rudenko, L, Kovalskyi, I, Kushnir, M, Tseluyko, V, Mostovoy, Y, Stanislavchuk, M, Kyiak, Y, Karpenko, Y, Malynovsky, Y, Klantsa, A, Kutniy, O, Amosova, E, Tashchuk, V, Leshchuk, O, Parkhomenko, A, Rishko, M, Kopytsya, M, Yagensky, A, Vatutin, M, Bagriy, A, Barna, OM, Ushakov, O, Dzyak, G, Goloborodko, B, Rudenko, A, Trevelyan, J, Zaman, A, Lee, K, Moriarty, A, Aggarwal, RK, Clifford, P, Wong, YK, Iqbal, SMR, Subkovas, E, Braganza, D, Sarkar, D, Storey, R, Griffiths, H, Mcclure, S, Muthusamy, R, Kurian, J, Levy, T, Barr, C, Kadr, H, Gerber, R, Simaitis, A, Soran, H, Mathur, A, Brodison, A, Oliver, R, Mudawi, T, Reynolds, T, Sharman, D, Butler, R, Wilkinson, P, Lip, GYH, Halcox, J, Vardi, G, Baldari, D, Brabham, D, Treasure, C, Dahl, C, Palmer, B, Wiseman, A, Puri, S, Mohart, AE, Ince, C, Flores, E, Wright, S, Cheng, SC, Rosenberg, M, Rogers, W, Kosinski, E, Forgosh, L, Waltman, J, Khan, M, Shoukfeh, M, Dagher, G, Lieber, I, Kumar, P, East, C, Krichmar, P, White, L, Knickelbine, T, Haldis, T, Gillespie, E, Suh, D, Arif, I, Akhter, F, Carlson, E, D'Urso, M, El-Ahdab, F, Nelson, W, Harris, B, Cohen, S, Carter, L, Sabatino, K, Haddad, T, Malik, A, Rao, S, Mulkay, A, Jovin, I, Klancke, K, Malhotra, V, Devarapalli, SK, Koren, M, Chandna, H, Dodds, G, Janik, M, Moran, J, Sumner, A, Kobayashi, J, Davis, W, Yazdani, S, Pasquini, J, Thakkar, M, Vedere, A, Leimbach, W, Rider, J, Singh, N, Shah, AV, Moriarty, PM, Janosik, D, Pepine, C, Berman, B, Gelormini, J, Daniels, C, Keating, F, Kondo, NI, Shetty, S, Waider, W, Takata, T, Abu-Fadel, M, Shah, V, Aggarwal, R, Izzo, M, Kumar, A, Hattler, B, Link, C, Bortnick, A, Kinzfogl, G, Ghitis, A, Larry, J, Teufel, E, Kuhlman, P, Mclaurin, B, Zhang, WW, Thew, S, Abbas, J, White, M, Ranadive, N, Gring, C, Henderson, D, Schuchard, T, Farhat, N, Kline, G, Mahal, S, Whitaker, J, Speirs, S, Andersen, R, Daboul, N, Horwitz, P, Jafar, Z, Mcgarvey, J, Panchal, V, Voyce, S, Blok, T, Sheldon, W, Azizad, MM, Schmalfuss, C, Picone, M, Herzog, W, Lindsey, J, Nowins, R, Lepor, N, El Shahawy, M, Weintraub, H, Irimpen, A, May, W, Galski, T, Chu, A, Mody, F, Hodes, Z, Fairlamb, J, Lambert, C, Raisinghani, A, Abbate, A, King, M, Carey, C, Gerber, J, Younis, L, Park, H, Vidovich, M, Knutson, T, Friedman, D, Chaleff, F, Loussararian, A, Kimmelstiel, C, Silver, K, Foster, M, Tonnessen, G, Amlani, M, Wali, A, Malozzi, C, Wattanakit, K, O'Donnell, PJ, Singal, D, Jaffrani, N, Banuru, S, Fisher, D, Xenakis, M, Perlmutter, N, Bhagwat, R, Strader, J, Akyea-Djamson, A, Labroo, A, Marais, HJ, Claxton, E, Berk, M, Rossi, P, Joshi, P, Khaira, AS, Kumkumian, G, Lupovitch, S, Purow, J, Welka, S, Hoffman, D, Fischer, S, Soroka, E, Eagerton, D, Pancholy, S, Ray, M, Farrar, M, Pollock, S, French, WJ, Diamantis, S, Gimple, L, Schwartz, S, Pereira, E, Spriggs, D, Strain, J, Vo, A, Chane, M, Hall, J, Vijay, N, Lotun, K, Lester, FM, Nahhas, A, Pope, T, Nager, P, Vohra, R, Bashir, R, Ahmed, H, Berlowitz, M, Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, PS, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Lui, H, Keen, W, Westerhausen, D, Khurana, S, Agarwal, H, Birchem, J, Penny, W, Chang, M, Gilbert, JM, Chalavarya, G, Eaton, C, Schmedtje, JF, Christenson, S, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Akright, L, Schifferdecker, B, Krawczyk, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, İÜC, and Ege Üniversitesi

Subjects
Male, medicine.medical_specialty, Acute coronary syndrome, alirocumab, 030204 cardiovascular system & hematology, Antibodies, Monoclonal, Humanized, lipids, PCSK9, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Double-Blind Method, coronary artery bypass graft, Internal medicine, medicine, Humans, Cardiac and Cardiovascular Systems, 030212 general & internal medicine, Myocardial infarction, cardiovascular diseases, Acute Coronary Syndrome, Coronary Artery Bypass, Alirocumab, Aged, Kardiologi, business.industry, Unstable angina, Hazard ratio, cholesterol, Middle Aged, medicine.disease, surgical procedures, operative, Bypass surgery, Cardiovascular Diseases, Cardiology, Drug Therapy, Combination, Female, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, business, Mace
Abstract

Sherwood, Matthew/0000-0002-4305-5883; Taskinen, Marja-Riitta/0000-0002-6229-3588; Leonardi, Sergio/0000-0002-4800-6132; Raffel, Owen C/0000-0001-5470-7050; Muenzel, Thomas/0000-0001-5503-4150; Ersanli, Murat/0000-0003-1847-3087; Gislason, Gunnar H/0000-0002-0548-402X; bastos, jose/0000-0002-9526-3123; Abbate, Antonio/0000-0002-1930-785X; Chumakova, Galina A/0000-0002-2810-6531; Nikolaev, Konstantin/0000-0003-4601-6203; Tse, Hung Fat/0000-0002-9578-7808; Keskin, Kudret/0000-0002-9049-1530; Reshetko, Olga/0000-0003-3107-7636; Podoleanu, Cristian/0000-0001-9987-2519; Aylward, Philip/0000-0002-5358-8552; LETIERCE, Alexia/0000-0001-6679-5772, WOS: 000483334800002, PubMed: 31466614, BACKGROUND Patients with acute coronary syndrome (ACS) and history of coronary artery bypass grafting (CABG) are at high risk for recurrent cardiovascular events and death. OBJECTIVES This study sought to determine the clinical benefit of adding alirocumab to statins in ACS patients with prior CABG in a pre-specified analysis of ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab). METHODS Patients (n = 18,924) 1 to 12 months post-ACS with elevated atherogenic lipoprotein levels despite high-intensity statin therapy were randomized to alirocumab or placebo subcutaneously every 2 weeks. Median follow-up was 2.8 years. the primary composite endpoint of major adverse cardiovascular events (MACE) comprised coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. Patients were categorized by CABG status: no CABG (n = 16,896); index CABG after qualifying ACS, but before randomization (n = 1,025); or CABG before the qualifying ACS (n = 1,003). RESULTS in each CABG category, hazard ratios (95% confidence intervals) for MACE (no CABG 0.86 [0.78 to 0.95], index CABG 0.85 [0.54 to 1.35], prior CABG 0.77 [0.61 to 0.98]) and death (0.88 [ 0.75 to 1.03], 0.85 [0.46 to 1.59], 0.67 [0.44 to 1.01], respectively) were consistent with the overall trial results (0.85 [ 0.78 to 0.93] and 0.85 [0.73 to 0.98], respectively). Absolute risk reductions (95% confidence intervals) differed across CABG categories for MACE (no CABG 1.3% [0.5% to 2.2%], index CABG 0.9% [-2.3% to 4.0%], prior CABG 6.4% [0.9% to 12.0%]) and for death (0.4% [-0.1% to 1.0%], 0.5% [-1.9% to 2.9%], and 3.6% [0.0% to 7.2%]). CONCLUSIONS Among patients with recent ACS and elevated atherogenic lipoproteins despite intensive statin therapy, alirocumab was associated with large absolute reductions in MACE and death in those with CABG preceding the ACS event. (ODYSSEY OUTCOMES: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402) (C) 2019 by the American College of Cardiology Foundation., Fondation Assistance Publique-Hopitaux de Paris, Paris, France, The authors thank the patients, study coordinators, and investigators who participated in this trial. Sophie Rushton-Smith, PhD (MedLink Healthcare Communications, London) provided editorial assistance in the preparation of the manuscript (limited to editing for style, referencing, and figure and table editing) and was funded by Fondation Assistance Publique-Hopitaux de Paris, Paris, France.

Published
2019

6. Effect of Alirocumab on Mortality After Acute Coronary Syndromes An Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial

Author

Steg, PG, Szarek, M, Bhatt, DL, Bittner, VA, Bregeault, M-F, Dalby, AJ, Diaz, R, Edelberg, JM, Goodman, SG, Hanotin, C, Harrington, RA, Jukema, JW, Lecorps, G, Mahaffey, KW, Moryusef, A, Ostadal, P, Parkhomenko, A, Pordy, R, Roe, MT, Tricoci, P, Vogel, R, White, HD, Zeiher, AM, Schwartz, GG, Sasiela, WJ, Tamby, J-F, Aylward, PE, Drexel, H, Sinnaeve, P, Dilic, M, Gotcheva, NN, Prieto, J-C, Yong, H, Lopez-Jaramillo, P, Pecin, I, Reiner, Z, Poulsen, SH, Viigimaa, M, Nieminen, MS, Danchin, N, Chumburidze, V, Marx, N, Liberopoulos, E, Valdovinos, PCM, Tse, H-F, Kiss, RG, Xavier, D, Zahger, D, Valgimigli, M, Kimura, T, Kim, HS, Kim, S-H, Kedev, S, Erglis, A, Laucevicius, A, Yusoff, K, Lopez, R, Ramos Lopez, GA, Alings, M, Halvorsen, S, Correa Flores, RM, Sy, RG, Budaj, A, Morais, J, Dorobantu, M, Karpov, Y, Ristic, AD, Chua, T, Murin, J, Fras, Z, Tunon, J, De Silva, HA, Hagstrom, E, Muller, C, Chiang, C-E, Sritara, P, Guneri, S, Ray, KK, Moriarty, PM, Chaitman, B, Kelsey, SF, Olsson, AG, Rouleau, J-L, Simoons, ML, Alexander, K, Meloni, C, Rosenson, R, Sijbrands, EJG, Alexander, JH, Armaganijan, L, Bagai, A, Bahit, MC, Brennan, JM, Clifton, S, DeVore, AD, Deloatch, S, Dickey, S, Dombrowski, K, Ducrocq, G, Eapen, Z, Endsley, P, Eppinger, A, Harrison, RW, Hess, CN, Hlatky, MA, Jordan, JD, Knowles, JW, Kolls, BJ, Kong, DF, Leonardi, S, Lillis, L, Maron, DJ, Marcus, J, Mathews, R, Mehta, RH, Mentz, RJ, Moreira, HG, Patel, CB, Pereira, SB, Perkins, L, Povsic, TJ, Puymirat, E, Jones, WS, Shah, BR, Sherwood, MW, Stringfellow, K, Sujjavanich, D, Toma, M, Van Diepen, SFP, Wilson, MD, Yan, AT-K, Lopes, RD, Trotter, C, Schiavi, LB, Garrido, M, Alvarisqueta, AF, Sassone, SA, Bordonava, AP, Alves De Lima, AE, Schmidberg, JM, Duronto, EA, Caruso, OC, Novaretto, LP, Angel Hominal, M, Montana, OR, Caccavo, A, Gomez Vilamajo, OA, Lorenzatti, AJ, Cartasegna, LR, Paterlini, GA, Mackinnon, IJ, Caime, GD, Amuchastegui, M, Salomone, R, Codutti, OR, Jure, HO, Bono, JOE, Hrabar, AD, Vallejos, JA, Ahuad Guerrero, RA, Novoa, F, Patocchi, CA, Zaidman, CJ, Giuliano, ME, Dran, RD, Vico, ML, Carnero, GS, Guzman, PN, Medrano Allende, JC, Garcia Brasca, DF, Bustamante Labarta, MH, Nani, S, Blumberg, EDS, Colombo, HR, Liberman, A, Luciardi, HL, Waisman, GD, Berli, MA, Duran, ROG, Cestari, HG, Luquez, HA, Giordano, JA, Saavedra, SS, Zapata, G, Costamagna, O, Llois, S, Waites, JH, Collins, N, Soward, A, Hii, CLS, Shaw, J, Arstall, MA, Horowitz, J, Rogers, JF, Colquhoun, D, Oqueli Flores, RE, Roberts-Thomson, P, Raffel, O, Lehman, SJ, Aroney, C, Coverdale, SGM, Garrahy, PJ, Starmer, G, Sader, M, Carroll, PA, Dick, R, Zweiker, R, Hoppe, U, Huber, K, Berger, R, Weidinger, F, Faes, D, Hermans, K, Pirenne, B, Leone, A, Hoffer, E, Vrolix, MCM, De Wolf, L, Wollaert, B, Castadot, M, Dujardin, K, Beauloye, C, Vervoort, G, Striekwold, H, Convens, C, Roosen, J, Barbato, E, Claeys, M, Cools, F, Terzic, I, Barakovic, F, Midzic, Z, Pojskic, B, Fazlibegovic, E, Durak-Nalbantic, A, Vulic, D, Muslibegovic, A, Goronja, B, Reis, G, Sousa, L, Nicolau, JC, Giorgeto, FE, Silva, RP, Maia, LN, Rech, R, Rossi, PRF, Cerqueira, MJAG, Duda, N, Kalil, R, Kormann, A, Abrantes, JAM, Pimentel Filho, P, Soggia, AP, De Santos, MON, Neuenschwander, F, Bodanese, LC, Michalaros, YL, Eliaschewitz, FG, Vidotti, MH, Leaes, PE, Botelho, RV, Kaiser, S, Fernandes Manenti, ERF, Precoma, DB, Moura Jorge, JC, Silva, PGMDB, Silveira, JA, Saporito, W, Marin Neto, JA, Feitosa, GS, Ritt, LEF, De Souza, JA, Costa, F, Souza, WKSB, Reis, HJL, Machado, L, Aidar Ayoub, JC, Todorov, GV, Nikolov, FP, Velcheva, ES, Tzekova, ML, Benov, HO, Petranov, SL, Tumbev, HS, Shehova-Yankova, NS, Markov, DT, Raev, DH, Mollov, MN, Kichukov, KN, Ilieva-Pandeva, KA, Ivanova, R, Mincheva, VM, Lazov, PV, Dimov, BI, Senaratne, M, Stone, J, Kornder, J, Pearce, S, Dion, D, Savard, D, Pesant, Y, Pandey, A, Robinson, S, Gosselin, G, Vizel, S, Hoag, G, Bourgeois, R, Morisset, A, Sabbah, E, Sussex, B, Kouz, S, MacDonald, P, Diaz, A, Michaud, N, Fell, D, Leung, R, Vuurmans, T, Lai, C, Nigro, F, Davies, R, Nogareda, G, Vijayaraghavan, R, Ducas, J, Lepage, S, Mehta, S, Cha, J, Dupuis, R, Fong, P, Rodes-Cabau, J, Fadlallah, H, Cleveland, D, Thao, H, Bata, I, Hameed, A, Pincetti, C, Potthoff, S, Prieto, JC, Acevedo, M, Aguirre, A, Vejar, M, Yanez, M, Araneda, G, Fernandez, M, Perez, L, Varleta, P, Florenzano, F, Huidobro, L, Raffo, CA, Olivares, C, Nahuelpan, L, Montecinos, H, Chen, J, Dong, Y, Huang, W, Wang, J, Huang, S, Yao, Z, Li, X, Cui, L, Lin, W, Sun, Y, Li, J, Zhang, X, Zhu, H, Chen, D, Huang, L, Dong, S, Su, G, Xu, B, Su, X, Cheng, X, Lin, J, Zong, W, Li, H, Feng, Y, Xu, D, Yang, X, Ke, Y, Lin, X, Zhang, Z, Zheng, Z, Luo, Z, Chen, Y, Ding, C, Zheng, Y, Peng, D, Li, Y, Wei, M, Liu, S, Yu, Y, Qu, B, Jiang, W, Zhou, Y, Zhao, X, Yuan, Z, Guo, Y, Xu, X, Shi, X, Ge, J, Fu, G, Bai, F, Fang, W, Shou, X, Lu, Q, Zhang, R, Zhu, J, Xu, Y, Fan, Z, Li, T, Wu, C, Jaramillo, N, Vallejo, GS, Botia, DCL, Lopez, RB, De Salazar, DIM, Bonfanti, AJC, Higuera, JD, Silva, SIB, Lozada, HJG, Arroyo, JAC, Mendoza, JLA, Ruiz, RLF, Jatin, FGM, Herazo, AS, Parada, JC, Triana, MAU, Strozzi, M, Car, S, Milicic, D, Bencic, ML, Pintaric, H, Prvulovic, D, Sikic, J, Persic, V, Mileta, D, Stambuk, K, Zdravko, B, Tomulic, V, Krstulovic, SM, Starcevic, B, Spinar, J, Horak, D, Stasek, J, Alan, D, Machova, V, Linhart, A, Novotny, V, Kaucak, V, Rokyta, R, Naplava, R, Coufal, Z, Adamkova, V, Podpera, I, Zizka, J, Motovska, Z, Marusincova, I, Svab, P, Heinc, P, Kuchar, J, Povolny, P, Matuska, J, Raungaard, B, Clemmensen, P, Bang, LE, May, O, Bottcher, M, Hove, JD, Frost, L, Gislason, G, Larsen, J, Johansen, PB, Hald, F, Jeppesen, J, Nielsen, T, Kristensen, KS, Walichiewicz, PM, Lomholdt, JD, Klausen, IC, Nielsen, PK, Davidsen, F, Videbaek, L, Soots, M, Vahula, V, Hedman, A, Soopold, U, Martsin, K, Kristjan, A, Taskinen, M-R, Porthan, K, Airaksinen, JK, Juonala, M, Kiviniemi, T, Vikman, S, Posio, P, Taurio, J, Huikuri, H, Kaikkonen, K, Coste, P, Ferrari, E, Morel, O, Montalescot, G, Barone-Rochette, G, Mansourati, J, Cottin, Y, Leclercq, F, Belhassane, A, Delarche, N, Boccara, F, Paganelli, F, Clerc, J, Schiele, F, Aboyans, V, Probst, V, Berland, J, Lefevre, T, Citron, B, Khintibidze, I, Shaburishvili, T, Pagava, Z, Ghlonti, R, Lominadze, Z, Khabeishvili, G, Hemetsberger, R, Rauch-Kroehnert, U, Stratmann, M, Appel, K-F, Schmidt, E, Omran, H, Stellbrink, C, Dorsel, T, Lianopoulos, E, Marx, R, Zirlik, A, Schellenberg, D, Heitzer, T, Laufs, U, Gielen, S, Winkelmann, B, Behrens, S, Sydow, K, Simonis, G, Muenzel, T, Werner, N, Leggewie, S, Boecker, D, Braun-Dullaeus, R, Toursarkissian, N, Jeserich, M, Weissbrodt, M, Schaeufele, T, Weil, J, Voeller, H, Waltenberger, J, Natour, M, Schmitt, S, Steiner, S, Heidenreich, L, Gremmler, U, Killat, H, Rieker, W, Patsilinakos, S, Kartalis, A, Manolis, A, Sionis, D, Skoumas, I, Athyros, V, Vardas, P, Parthenakis, F, Alexopoulos, D, Hahalis, G, Lekakis, J, Hatzitolios, A, Ovando, SRF, Benecke, JLA, De Leon, ERR, Yan, BPY, Siu, DCW, Turi, T, Merkely, B, Ungi, I, Lupkovics, G, Nagy, L, Katona, A, Edes, I, Muller, G, Horvath, I, Kapin, T, Falukozy, J, Kumbla, M, Sandhu, M, Annam, S, Proddutur, NR, Premchand, RK, Mahajan, A, Abhyanakar, AD, Kerkar, P, Govinda, RA, Oomman, A, Sinha, D, Patil, SN, Kahali, D, Sawhney, J, Joshi, AB, Chaudhary, S, Harkut, P, Guha, S, Porwal, S, Jujjuru, S, Pothineni, RB, Monteiro, MR, Khan, A, Iyengar, SS, Grewal, JS, Chopda, M, Fulwani, MC, Patange, A, Chopra, VK, Goyal, NK, Shinde, R, Manakshe, GV, Patki, N, Sethi, S, Munusamy, V, Karna, S, Adhyapak, S, Pandurangi, U, Mathur, R, Kalashetti, S, Bhagwat, A, Raghuraman, B, Yerra, SK, Bhansali, P, Borse, R, Das, S, Abdullakutty, J, Saathe, S, Palimkar, P, Abdullkutty, J, Sathe, S, Atar, S, Shechter, M, Mosseri, M, Arbel, Y, Lotan, C, Rosenschein, U, Katz, A, Henkin, Y, Francis, A, Klutstein, M, Nikolsky, E, Turgeman, Y, Halabi, M, Kornowski, R, Jonas, M, Amir, O, Rozenman, Y, Fuchs, S, Hussein, O, Gavish, D, Vered, Z, Caraco, Y, Elias, M, Tov, N, Lishner, M, Elias, N, Piovaccari, G, De Pellegrin, A, Guardigli, G, Licciardello, G, Auguadro, C, Cuccia, C, Salvioni, A, Musumeci, G, Calabro, P, Novo, S, Faggiano, P, De Cesare, NB, Berti, S, Cavallini, C, Puccioni, E, Galvani, M, Tespili, M, Piatti, P, Palvarini, M, De Luca, G, Violini, R, De Leo, A, Filardi, PP, Ferratini, M, Ricca, V, Dai, K, Kamiya, H, Ando, K, Takeda, Y, Morino, Y, Hata, Y, Kimura, K, Kishi, K, Michishita, I, Uehara, H, Higashikata, T, Hirayama, A, Hirooka, K, Sakagami, S, Taguchi, S, Koike, A, Fujinaga, H, Koba, S, Kozuma, K, Kawasaki, T, Ono, Y, Shimizu, M, Katsuda, Y, Wada, A, Shinke, T, Ako, J, Fujii, K, Takahashi, T, Sakamoto, T, Furukawa, Y, Sugino, H, Mano, T, Utsu, N, Ito, K, Haraguchi, T, Ueda, Y, Nishibe, A, Fujimoto, K, Masutani, M, Yoon, JH, Park, HS, Chae, I-H, Kim, MH, Jeong, MH, Rha, S, Kim, C, Kim, H-S, Hong, T, Tahk, S-J, Kim, Y, Busmane, A, Pontaga, N, Strelnieks, A, Mintale, I, Sime, I, Petrulioniene, Z, Kavaliauskiene, R, Jurgaitiene, R, Sakalyte, G, Slapikas, R, Norkiene, S, Misonis, N, Kibarskis, A, Kubilius, R, Bojovski, S, Lozance, N, Kjovkaroski, A, Doncovska, S, Ong, TK, Kasim, S, Maskon, O, Kandasamy, B, Liew, HB, Mohamed, WMIW, Garcia Castillo, A, Carrillo Calvillo, J, Fajardo Campos, P, Nunez Fragoso, JC, Bayram Llamas, EA, Alcocer Gamba, MA, Carranza Madrigal, J, Gonzalez Salas, LG, Lopez Rosas, E, Gonzalez Diaz, B, Salcido Vazquez, E, Nacoud Ackar, A, Llamas Esperon, GA, Martinez Sanchez, CR, Guerrero De Leon, M, Suarez Otero, R, Fanghanel Salmon, G, Perez Rios, JA, Garza Ruiz, JA, Breedveld, RW, Hoogslag, PAM, Suryapranata, H, Oomen, A, Wiersma, JJ, Van Der Wal, RMA, Van Huysduynen-Monraats, PSH, Karalis, I, Verdel, GJE, Brueren, BRG, Troquay, RP, Viergever, EP, Al-Windy, NYY, Bartels, GL, Cornel, JH, Hermans, WRM, Herrman, JPR, Bos, RJ, Groutars, RGEJ, Van Der Zwaan, CC, Kaplan, R, Ronner, E, Groenemeijer, BE, Bronzwaer, PNA, Liem, AAH, Rensing, BJWM, Bokern, MJJA, Nijmeijer, R, Hersbach, FMRJ, Willems, FF, Gosselink, ATM, Elliott, J, Wilkins, G, Fisher, R, Scott, D, Hart, H, Stewart, R, Harding, S, Ternouth, I, Fisher, N, Aitken, D, Anscombe, R, Davidson, L, Tomala, T, Nygard, O, Sparby, JA, Andersen, K, Gullestad, L, Jortveit, J, Munk, PS, Singsaas, EG, Hurtig, U, Calderon Ticona, JR, Durand Velasquez, JR, Negron Miguel, SA, Sanabria Perez, ES, Carrion Chambilla, JM, Chavez Ayala, CA, Castillo Leon, RP, Vargas Gonzales, RJ, Hernandez Zuniga, JD, Camacho Cosavalente, LA, Bravo Mannucci, JE, Heredia Landeo, J, Llerena Navarro, NC, Roldan Concha, YM, Rodriguez Chavez, V-CE, Anchante Hernandez, HA, Zea Nunez, CA, Mogrovejo Ramos, W, Ferrolino, A, Sy, RAG, Tirador, L, Matiga, G, Coching, RM, Bernan, A, Rogelio, G, Morales, DD, Tan, E, Sulit, DJ, Wlodarczak, A, Jaworska, K, Skonieczny, G, Pawlowicz, L, Wojewod, P, Busz-Papiez, B, Bednarski, J, Goch, A, Staneta, P, Dulak, E, Saminsk, K, Krasowski, W, Sudnik, W, Zurakowski, A, Skorski, M, Lysek, R, Miklaszewicz, B, Kubica, J, Lipko, JA, Kostarska-Srokosz, E, Piepiorka, M, Drzewiecka, A, Sciborski, R, Stasiewski, A, Blicharski, T, Bystryk, L, Szpajer, M, Korol, M, Czerski, T, Mirek-Bryniarska, E, Gniot, J, Lubinski, A, Gorny, J, Franek, E, Raczak, G, Szwed, H, Monteiro, P, Bastos, JM, Pereira, HH, Martins, D, Seixo, F, Mendonca, C, Botelho, A, Minescu, B, Istratoaie, O, Tesloianu, DN, Cristian, G, Podoleanu, CGC, Constantinescu, MCA, Bengus, CM, Militaru, C, Rosu, D, Parepa, IR, Matei, AV, Alexandru, TM, Coman, I, Cioranu, RS, Dimulescu, D, Shvarts, Y, Orlikova, O, Kobalava, Z, Barbarash, OL, Markov, V, Lyamina, N, Gordienko, A, Zrazhevsky, K, Vishnevsky, AY, Gurevich, V, Stryuk, R, Lomakin, NV, Bokarev, I, Shalaev, S, Khaisheva, L, Chizhov, P, Viktorova, I, Osokina, N, Akatova, E, Chumakova, G, Libov, I, Voevoda, MI, Tretyakova, TV, Baranov, E, Shustov, S, Yakushin, S, Gordeev, I, Khasanov, N, Reshetko, O, Sotnikova, T, Molchanova, O, Nikolaev, K, Gapon, L, Baranova, E, Shogenov, Z, Kosmachova, E, Povzun, A, Egorova, L, Tyrenko, VV, Ivanov, IG, Kanorsky, S, Simic, D, Ivanovic, N, Davidovic, G, Tasic, N, Asanin, MR, Stojic, S, Apostolovic, SR, Ilic, S, Putnikovic, B, Stankovic, A, Arandjelovic, A, Radovanovic, S, Balinovac, J, Dincic, DV, Seferovic, P, Dodic, S, Dimkovic, S, Poh, K-K, Ong, HY, Micko, K, Nociar, J, Pella, D, Fulop, P, Hranai, M, Palka, J, Mazur, J, Majercak, I, Dzupina, A, Fazekas, F, Gonsorcik, J, Bugan, V, Selecky, J, Kamensky, G, Strbova, J, Smik, R, Dukat, A, Olexa, P, Zuran, I, Poklukar, J, Suligoj, NC, Cevc, M, Cyster, HP, Ranjith, N, Corbett, C, Bayat, J, Makotoko, EM, Kapp, IE, Basson, MMDV, Lottering, H, Van Zyl, LJ, Sebastian, PJ, Pillay, T, Saaiman, JA, Commerford, PJ, Cassimjee, S, Ebrahim, IO, Sarvan, M, Mynhardt, JH, Reuter, H, Moodley, R, Vida, M, Cequier Fillat, AR, Peris, VB, Jimenez, FF, Marin, F, Cruz Fernandez, JM, Gil-Extremera, B, Diz, FW, Garcia-Dorado, D, Iniguez, A, Tunon Fernandez, J, Gonzalez-Juanatey, JR, Fernandez Portales, J, Civeira Murillo, F, Matas Pericas, L, Luis Zamorano, J, De Mora Martin, M, Bruguera Cortada, J, Alonso Martin, JJ, De Berrazueta Fernandez, JR, Diaz Fernandez, JF, Garcia Lledo, JA, Cosin Sales, J, Botas Rodriguez, J, Gusi Tragant, G, Benedicto, A, Gonzalez-Juanatey, C, Camprubi Potau, M, Plaza Perez, I, Moris De La Tassa, C, Loma-Osorio Rincon, P, Balaguer Recena, J, Escudier, JM, Coca Payeras, A, Alonso Orcajo, N, Valdivielso, P, Constantine, G, Haniffa, R, Tissera, N, Amarasekera, S, Fernando, N, Jayawardena, J, Santharaj, W, Ekanayaka, R, Mendis, S, Senaratne, V, Mayurathan, G, Sirisena, T, Rajapaksha, A, Herath, JI, Amarasena, N, Berglund, S, Rasmanis, G, Witt, N, Mourtzinis, G, Nicol, P, Hansen, O, Romeo, S, Jensen, SA, Torstensson, I, Ahremark, U, Sundelin, T, Moccetti, T, Mach, F, Binder, R, Tsai, W-C, Ueng, K-C, Lai, W-T, Liu, M-E, Hwang, J-J, Yin, W-H, Hsieh, I-C, Lin, WH, Kuo, J-Y, Huang, T-Y, Fang, C-Y, Kaewsuwanna, P, Soonfuang, W, Jintapakorn, W, Sukonthasarn, A, Wongpraparut, N, Sastravaha, K, Sansanayudh, N, Kehasukcharoen, W, Piyayotai, D, Chotnoparatpat, P, Camsari, A, Kultursay, H, Mutlu, B, Ersanli, M, Demirtas, M, Kirma, C, Ural, E, Koldas, L, Karpenko, O, Prokhorov, A, Vakaluyk, I, Myshanych, H, Reshotko, D, Batushkin, V, Rudenko, L, Kovalskyi, I, Kushnir, M, Tseluyko, V, Mostovoy, Y, Stanislavchuk, M, Kyiak, Y, Karpenko, Y, Malynovsky, Y, Klantsa, A, Kutniy, O, Amosova, E, Tashchuk, V, Leshchuk, O, Rishko, M, Kopytsya, M, Yagensky, A, Vatutin, M, Bagriy, A, Barna, OM, Ushakov, O, Dzyak, G, Goloborodko, B, Rudenko, A, Zheleznyy, V, Trevelyan, J, Zaman, A, Lee, K, Moriarty, A, Aggarwal, RK, Clifford, P, Wong, Y-K, Iqbal, SMR, Subkovas, E, Braganza, D, Sarkar, D, Storey, R, Griffiths, H, Mcclure, S, Muthusamy, R, Kurian, J, Levy, T, Barr, C, Kadr, H, Gerber, R, Simaitis, A, Soran, H, Mathur, A, Brodison, A, Oliver, R, Mudawi, T, Reynolds, T, Sharman, D, Butler, R, Wilkinson, P, Lip, GYH, Halcox, J, Vardi, G, Baldari, D, Brabham, D, Treasure, C, Dahl, C, Palmer, B, Wiseman, A, Puri, S, Mohart, AE, Ince, C, Flores, E, Wright, S, Cheng, S-C, Rosenberg, M, Rogers, W, Kosinski, E, Forgosh, L, Waltman, J, Khan, M, Shoukfeh, M, Dagher, G, Lieber, I, Kumar, P, East, C, Krichmar, P, White, L, Knickelbine, T, Haldis, T, Gillespie, E, Suh, D, Arif, I, Akhter, F, Carlson, E, D'Urso, M, El-Ahdab, F, Nelson, W, Harris, B, Cohen, S, Carter, L, Sabatino, K, Haddad, T, Malik, A, Rao, S, Mulkay, A, Jovin, I, Klancke, K, Malhotra, V, Devarapalli, SK, Koren, M, Chandna, H, Dodds, G, Janik, M, Moran, J, Sumner, A, Kobayashi, J, Davis, W, Yazdani, S, Pasquini, J, Thakkar, M, Vedere, A, Leimbach, W, Rider, J, Singh, N, Shah, AV, Janosik, D, Pepine, C, Berman, B, Gelormini, J, Daniels, C, Keating, F, Kondo, NI, Shetty, S, Waider, W, Takata, T, Abu-Fadel, M, Shah, V, Aggarwal, R, Izzo, M, Kumar, A, Hattler, B, Link, C, Bortnick, A, Kinzfogl, G, Ghitis, A, Larry, J, Teufel, E, Kuhlman, P, Mclaurin, B, Zhang, W, Thew, S, Abbas, J, White, M, Ranadive, N, Gring, C, Henderson, D, Schuchard, T, Farhat, N, Kline, G, Mahal, S, Whitaker, J, Speirs, S, Andersen, R, Daboul, N, Horwitz, P, Ponce, G, Jafar, Z, Mcgarvey, J, Panchal, V, Voyce, S, Blok, T, Sheldon, W, Azizad, MM, Schmalfuss, C, Picone, M, Herzog, W, Lindsey, J, Nowins, R, Lepor, N, El Shahawy, M, Weintraub, H, Irimpen, A, May, W, Galski, T, Chu, A, Mody, F, Hodes, Z, Rose, G, Fairlamb, J, Lambert, C, Raisinghani, A, Abbate, A, King, M, Carey, C, Gerber, J, Younis, L, Park, HT, Vidovich, M, Knutson, T, Friedman, D, Chaleff, F, Loussararian, A, Rozeman, P, Kimmelstiel, C, Silver, K, Foster, M, Tonnessen, G, Amlani, M, Wali, A, Malozzi, C, Wattanakit, K, O'Donnell, PJ, Singal, D, Jaffrani, N, Banuru, S, Fisher, D, Xenakis, M, Perlmutter, N, Bhagwat, R, Strader, J, Akyea-Djamson, A, Labroo, A, Marais, HJ, Claxton, E, Berk, M, Rossi, P, Joshi, P, Khaira, AS, Kumkumian, G, Lupovitch, S, Purow, J, Welka, S, Hoffman, D, Fischer, S, Soroka, E, Eagerton, D, Pancholy, S, Ray, M, Farrar, M, Pollock, S, French, WJ, Diamantis, S, Gimple, L, Neustel, M, Schwartz, S, Pereira, E, Spriggs, D, Strain, J, Vo, A, Chane, M, Hall, J, Vijay, N, Lotun, K, Lester, FM, Nahhas, A, Pope, T, Nager, P, Vohra, R, Bashir, R, Ahmed, H, Berlowitz, M, Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, PS, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Lui, H, Keen, W, Westerhausen, D, Khurana, S, Agarwal, H, Birchem, J, Penny, W, Chang, M, Murphy, S, Schifferdecker, B, Gilbert, JM, Chalavarya, G, Eaton, C, Schmedtje, JF, Christenson, S, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Akright, L, Krawczyk, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, Camp, A, Lopes, R, Egydio, F, Kawakami, A, Oliveira, J, Wozniak, J, Matthews, A, Ratky, C, Valiris, J, Berdan, L, Hepditch, A, Quintero, K, Rorick, T, Westbrook, M, Pascual, A, Rovito, C, Bezault, M, Drouet, E, Simon, T, Alsweiler, C, Luyten, A, Aylward, P, Butters, J, Griffith, L, Shaw, M, Grunberg, L, Islam, S, Bougon, N, Faustino, D, Fontecave, S, Murphy, J, Verrier, M, Agnetti, V, Andersen, D, Badreddine, E, Bekkouche, M, Bouancheau, C, Brigui, I, Brocklehurst, M, Cianciarulo, J, Devaul, D, Domokos, S, Gache, C, Gobillot, C, Guillou, S, Healy, J, Heath, M, Jaiwal, G, Javierre, C, Labeirie, J, Monier, M, Morales, U, Mrabti, A, Mthombeni, B, Okan, B, Smith, L, Sheller, J, Sopena, S, Pellan, V, Benbernou, F, Bengrait, N, Lamoureux, M, Kralova, K, Scemama, M, Bejuit, R, Coulange, A, Berthou, C, Repincay, J, Lorenzato, C, Etienne, A, Gouet, V, Loizeau, V, Normand, M, Ourliac, A, Rondel, C, Adamo, A, Beltran, P, Barraud, P, Dubois-Gache, H, Halle, B, Metwally, L, Mourgues, M, Sotty, M, Vincendet, M, Cotruta, R, Zhu, C, Fournie-Lloret, D, Morrello, C, Perthuis, A, Picault, P, Zobouyan, I, ODYSSEY OUTCOMES Comm, İÜC, Ege Üniversitesi, Rushton-Smith, Sophie, and ODYSSEY OUTCOMES Committees and Investigators

Subjects
Male, Cardiac & Cardiovascular Systems, MONOCLONAL-ANTIBODY, alirocumab, Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage, law.invention, PCSK9, chemistry.chemical_compound, Randomized controlled trial, law, Cardiac and Cardiovascular Systems, 1102 Cardiorespiratory Medicine and Haematology, Hypercholesterolemia/blood, Kardiologi, Hazard ratio, Middle Aged, Treatment Outcome, SAFETY, Cardiology, Female, Drug Therapy, Combination, Cholesterol, LDL/antagonists & inhibitors, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, REDUCING LIPIDS, Akutes Koronarsyndrom, acute coronary syndrome, cholesterol, mortality, PCSK9 protein, Antibodies, Monoclonal, Humanized/administration & dosage, medicine.medical_specialty, Acute coronary syndrome, Injections, Subcutaneous, Hypercholesterolemia, Placebo, Antibodies, Monoclonal, Humanized, 1117 Public Health and Health Services, Sterblichkeit, Double-Blind Method, Physiology (medical), Internal medicine, medicine, Humans, ddc:610, Alirocumab, Aged, Science & Technology, Cholesterol, business.industry, EVOLOCUMAB, 1103 Clinical Sciences, Cholesterol, LDL, medicine.disease, EFFICACY, Increased risk, chemistry, Peripheral Vascular Disease, Cardiovascular System & Hematology, Cardiovascular System & Cardiology, Acute Coronary Syndrome/blood, Cholesterin, Human medicine, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Follow-Up Studies
Abstract

bastos, jose/0000-0002-9526-3123; Manakshe, Gajendra/0000-0002-4983-4271; Tse, Hung Fat/0000-0002-9578-7808; Gislason, Gunnar H/0000-0002-0548-402X; Taskinen, Marja-Riitta/0000-0002-6229-3588; Racca, Vittorio/0000-0002-4465-3789; Keskin, Kudret/0000-0002-9049-1530; Sherwood, Matthew/0000-0002-4305-5883; Sandhu, Manjinder/0000-0003-2538-2079; Nikolaev, Konstantin/0000-0003-4601-6203; Ersanli, Murat/0000-0003-1847-3087; Raffel, Owen C/0000-0001-5470-7050; Abbate, Antonio/0000-0002-1930-785X; Muenzel, Thomas/0000-0001-5503-4150; Leonardi, Sergio/0000-0002-4800-6132; Chumakova, Galina A/0000-0002-2810-6531; Podoleanu, Cristian/0000-0001-9987-2519; Pereira, Helder/0000-0001-8656-4883; Reshetko, Olga/0000-0003-3107-7636, WOS: 000476768100007, PubMed: 31117810, Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. in a prespecified analysis of 8242 patients eligible for >= 3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P= 100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; P-interaction=0.007). in the alirocumab group, all-cause death declined with achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for >= 3 years, if baseline LDL-C is >= 100 mg/dL, or if achieved LDL-C is low., Sanofi; Regeneron Pharmaceuticals, Inc., The trial was funded by Sanofi and Regeneron Pharmaceuticals, Inc.

Published
2019

7. Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial

Author

Ray KK, Colhoun HM, Szarek M, Baccara-Dinet M, Bhatt DL, Bittner VA, Budaj AJ, Diaz R, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Loizeau V, Lopes RD, Moryusef A, Murin J, Pordy R, Ristic AD, Roe MT, Tuñón J, White HD, Zeiher AM, Schwartz GG, Steg PG, ODYSSEY OUTCOMES Committees and Investigators, and Lovric Bencic, M.

Subjects
diabetes mellitus, alirocuma, acute coronary syndrome outcomes
Abstract

ODYSSEY OUTCOMES was a randomised, double-blind, placebo- controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1–12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1:1) to receive alirocumab or placebo every 2 weeks ; randomisation was stratified by country and was done centrally with an interactive voice- response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0·65–1·30 mmol/L. In this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)—defined on the basis of patient history, review of medical records, or baseline HbA1cor fasting serum glucose—and risk of new-onset diabetes among those without diabetes at baseline. The primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials.gov, number NCT01663402.

Published
2019

8. Alirocumab Reduces Total Hospitalizations and Increases Days Alive and Out of Hospital in the ODYSSEY OUTCOMES Trial

Author

DiCenso, D, Gotcheva, N, Sourdille, T, White, HD, Schwartz, GG, Steg, PG, Bhatt, DL, Bittner, VA, Diaz, R, Harrington, RA, Jukema, JW, Szarek, M, Zeiher, AM, Tricoci, P, Mahaffey, KW, Edelberg, JM, Hanotin, C, Lecorps, G, Moryusef, A, Pordy, R, Sasiela, WJ, Drexel, H, Sinnaeve, P, Dilic, M, Gotcheva, NN, Goodman, SG, Prieto, JC, Yong, H, Lopez-Jaramillo, P, Pecin, I, Reiner, Z, Poulsen, SH, Viigimaa, M, Nieminen, MS, Danchin, N, Chumburidze, V, Tse, HF, Xavier, D, Zahger, D, Valgimigli, M, Kim, HS, Erglis, A, Laucevicius, A, Lopez, R, Lopez, GAR, Alings, M, Chua, T, Murin, J, Fras, Z, Dalby, AJ, Tunon, J, De Silva, HA, Chiang, CE, Sritara, P, Guneri, S, Parkhomenko, A, Ray, KK, Moriarty, PM, Roe, MT, Chaitman, B, Kelsey, SF, Olsson, AG, Rouleau, JL, Simoons, ML, Alexander, K, Meloni, C, Rosenson, R, Sijbrands, EJG, Alexander, JH, Armaganijan, L, Bagai, A, Bahit, MC, Brennan, JM, Clifton, S, DeVore, AD, Deloatch, S, Dickey, S, Dombrowski, K, Ducrocq, G, Eapen, Z, Endsley, P, Eppinger, A, Harrison, RW, Hess, CN, Hlatky, MA, Jordan, JD, Knowles, JW, Kolls, BJ, Kong, DF, Leonardi, S, Lillis, L, Maron, DJ, Marcus, J, Mathews, R, Mehta, RH, Mentz, RJ, Moreira, HG, Patel, CB, Pereira, SB, Perkins, L, Povsic, TJ, Puymirat, E, Jones, WS, Shah, BR, Sherwood, MW, Stringfellow, K, Sujjavanich, D, Toma, M, Van Diepen, SFP, Wilson, MD, Yan, ATK, Lopes, RD, Trotter, C, Schiavi, LB, Garrido, M, Alvarisqueta, AF, Sassone, SA, Bordonava, AP, De Lima, AEA, Schmidberg, JM, Duronto, EA, Caruso, OC, Novaretto, LP, Hominal, MA, Montana, OR, Caccavo, A, Vilamajo, OAG, Lorenzatti, AJ, Cartasegna, LR, Paterlini, GA, Mackinnon, IJ, Caime, GD, Amuchastegui, M, Salomone, R, Codutti, OR, Jure, HO, Bono, JOE, Hrabar, AD, Vallejos, JA, Guerrero, RAA, Novoa, F, Patocchi, CA, Zaidman, CJ, Giuliano, ME, Dran, RD, Vico, ML, Carnero, GS, Guzman, PN, Allende, JCM, Brasca, DFG, Labarta, MHB, Nani, S, Blumberg, EDS, Colombo, HR, Liberman, A, Luciardi, HL, Waisman, GD, Berli, MA, Duran, ROG, Cestari, HG, Luquez, HA, Giordano, JA, Saavedra, SS, Zapata, G, Costamagna, O, Llois, S, Waites, JH, Collins, N, Soward, A, Aylward, PE, Hii, CLS, Shaw, J, Arstall, MA, Horowitz, J, Rogers, JF, Colquhoun, D, Flores, REO, Roberts-Thomson, P, Raffel, O, Lehman, SJ, Aroney, C, Coverdale, SGM, Garrahy, PJ, Starmer, G, Sader, M, Carroll, PA, Dick, R, Zweiker, R, Hoppe, U, Huber, K, Berger, R, Weidinger, F, Faes, D, Hermans, K, Pirenne, B, Leone, A, Hoffer, E, Vrolix, MCM, De Wolf, L, Wollaert, B, Castadot, M, Dujardin, K, Beauloye, C, Vervoort, G, Striekwold, H, Convens, C, Roosen, J, Barbato, E, Claeys, M, Cools, F, Terzic, I, Barakovic, F, Midzic, Z, Pojskic, B, Fazlibegovic, E, Durak-Nalbantic, A, Vulic, D, Muslibegovic, A, Goronja, B, Reis, G, Sousa, L, Nicolau, JC, Giorgeto, FE, Silva, RP, Maia, LN, Rech, R, Rossi, PRF, Cerqueira, MJAG, Duda, N, Kalil, R, Kormann, A, Abrantes, JAM, Pimentel, P, Soggia, AP, de Santos, MON, Neuenschwander, F, Bodanese, LC, Michalaros, YL, Eliaschewitz, FG, Vidotti, MH, Leaes, PE, Botelho, RV, Kaiser, S, Manenti, ERFF, Precoma, DB, Jorge, JCM, Silva, PGMD, Silveira, JA, Saporito, W, Marin, JA, Feitosa, GS, Ritt, LEF, de Souza, JA, Costa, F, Souza, WKSB, Reis, HJL, Machado, L, Ayoub, JCA, Todorov, GV, Nikolov, FP, Velcheva, ES, Tzekova, ML, Benov, HO, Petranov, SL, Tumbev, HS, Shehova-Yankova, NS, Markov, DT, Raev, DH, Mollov, MN, Kichukov, KN, Ilieva-Pandeva, KA, Ivanova, R, Mincheva, VM, Lazov, PV, Dimov, BI, Senaratne, M, Stone, J, Kornder, J, Pearce, S, Dion, D, Savard, D, Pesant, Y, Pandey, A, Robinson, S, Gosselin, G, Vizel, S, Hoag, G, Bourgeois, R, Morisset, A, Sabbah, E, Sussex, B, Kouz, S, MacDonald, P, Diaz, A, Michaud, N, Fell, D, Leung, R, Vuurmans, T, Lai, C, Nigro, F, Davies, R, Nogareda, G, Vijayaraghavan, R, Ducas, J, Lepage, S, Mehta, S, Cha, J, Dupuis, R, Fong, P, Rodes-Cabau, J, Fadlallah, H, Cleveland, D, Huynh, T, Bata, I, Hameed, A, Pincetti, C, Potthoff, S, Acevedo, M, Aguirre, A, Vejar, M, Yanez, M, Araneda, G, Fernandez, M, Perez, L, Varleta, P, Florenzano, F, Huidobro, L, Raffo, CA, Olivares, C, Nahuelpan, L, Montecinos, H, Chen, JY, Dong, YG, Huang, WJ, Wang, JZ, Huang, SA, Yao, ZH, Li, X, Cui, L, Lin, WH, Sun, YM, Wang, JF, Li, JP, Zhang, XL, Zhu, H, Chen, D, Huang, L, Dong, SH, Su, GH, Xu, BA, Su, X, Cheng, XS, Lin, JX, Zong, WX, Li, HM, Feng, Y, Xu, DL, Yang, XC, Ke, YN, Lin, XF, Zhang, Z, Zheng, ZQ, Luo, ZR, Chen, YD, Ding, CH, Zheng, Y, Li, XD, Peng, DQ, Li, Y, Wei, M, Liu, SW, Yu, YH, Qu, BM, Jiang, WH, Zhou, YJ, Zhao, XS, Yuan, ZY, Guo, Y, Xu, XP, Shi, XB, Ge, JB, Fu, GS, Bai, F, Fang, WY, Shou, XL, Yang, XJ, Wang, JA, Sun, YX, Lu, QH, Zhang, RY, Zhu, JH, Xu, YZ, Fan, ZC, Li, TC, Wu, C, Jaramillo, N, Vallejo, GS, Botia, DCL, Lopez, RB, De Salazar, DIM, Bonfanti, AJC, Higuera, JD, Silva, SIB, Lozada, HJG, Arroyo, JAC, Mendoza, JLA, Ruiz, RLF, Jatin, FGM, Herazo, AS, Parada, JC, Triana, MAU, Strozzi, M, Car, S, Milicic, D, Bencic, ML, Pintaric, H, Prvulovic, D, Sikic, J, Persic, V, Mileta, D, Stambuk, K, Zdravko, B, Tomulic, V, Krstulovic, SM, Starcevic, B, Spinar, J, Horak, D, Stasek, J, Alan, D, Machova, V, Linhart, A, Novotny, V, Kaucak, V, Rokyta, R, Naplava, R, Coufal, Z, Adamkova, V, Podpera, I, Zizka, J, Motovska, Z, Marusincova, I, Svab, P, Ostadal, P, Heinc, P, Kuchar, J, Povolny, P, Matuska, J, Raungaard, B, Clemmensen, P, Bang, LE, May, O, Bottcher, M, Hove, JD, Frost, L, Gislason, G, Larsen, J, Johansen, PB, Hald, F, Jeppesen, J, Nielsen, T, Kristensen, KS, Walichiewicz, PM, Lomholdt, JD, Klausen, IC, Nielsen, PK, Davidsen, F, Videbaek, L, Soots, M, Vahula, V, Hedman, A, Soopold, U, Martsin, K, Kristjan, A, Taskinen, MR, Porthan, K, Airaksinen, JK, Juonala, M, Kiviniemi, T, Vikman, S, Posio, P, Taurio, J, Huikuri, H, Kaikkonen, K, Coste, P, Ferrari, E, Morel, O, Montalescot, G, Barone-Rochette, G, Mansourati, J, Cottin, Y, Leclercq, F, Belhassane, A, Delarche, N, Boccara, F, Paganelli, F, Clerc, J, Schiele, F, Aboyans, V, Probst, V, Berland, J, Lefevre, T, Citron, B, Khintibidze, I, Shaburishvili, T, Pagava, Z, Ghlonti, R, Lominadze, Z, Khabeishvili, G, Hemetsberger, R, Rauch-Krohnert, U, Stratmann, M, Appel, KF, Schmidt, E, Omran, H, Stellbrink, C, Dorsel, T, Lianopoulos, E, Marx, R, Zirlik, A, Schellenberg, D, Heitzer, T, Laufs, U, Marx, N, Gielen, S, Winkelmann, B, Behrens, S, Sydow, K, Simonis, G, Muenzel, T, Werner, N, Leggewie, S, Bocker, D, Braun-Dullaeus, R, Toursarkissian, N, Jeserich, M, Weissbrodt, M, Schaeufele, T, Weil, J, Voller, H, Waltenberger, J, Natour, M, Schmitt, S, Steiner, S, Heidenreich, L, Gremmler, U, Killat, H, Rieker, W, Patsilinakos, S, Kartalis, A, Manolis, A, Sionis, D, Liberopoulos, E, Skoumas, I, Athyros, V, Vardas, P, Parthenakis, F, Alexopoulos, D, Hahalis, G, Lekakis, J, Hatzitolios, A, Ovando, SRF, Valdovinos, PCM, Benecke, JLA, De Leon, ERR, Yan, BPY, Siu, DCW, Turi, T, Merkely, B, Kiss, RG, Ungi, I, Lupkovics, G, Nagy, L, Katona, A, Edes, I, Muller, G, Horvath, I, Kapin, T, Falukozy, J, Kumbla, M, Sandhu, M, Annam, S, Proddutur, NR, Premchand, RK, Mahajan, A, Abhyanakar, AD, Kerkar, P, Govinda, RA, Oomman, A, Sinha, D, Patil, SN, Kahali, D, Sawhney, J, Joshi, AB, Chaudhary, S, Harkut, P, Guha, S, Porwal, S, Jujjuru, S, Pothineni, RB, Monteiro, MR, Khan, A, Iyengar, SS, Grewal, JS, Chopda, M, Fulwani, MC, Patange, A, Chopra, VK, Goyal, NK, Shinde, R, Manakshe, GV, Patki, N, Sethi, S, Munusamy, V, Karna, S, Adhyapak, S, Pandurangi, U, Mathur, R, Kalashetti, S, Bhagwat, A, Raghuraman, B, Yerra, SK, Bhansali, P, Borse, R, Das, S, Abdullakutty, J, Saathe, S, Abdullkutty, J, Sathe, S, Palimkar, P, Atar, S, Shechter, M, Mosseri, M, Arbel, Y, Lotan, C, Rosenschein, U, Katz, A, Henkin, Y, Francis, A, Klutstein, M, Nikolsky, E, Turgeman, Y, Halabi, M, Kornowski, R, Jonas, M, Amir, O, Rozenman, Y, Fuchs, S, Hussein, O, Gavish, D, Vered, Z, Caraco, Y, Elias, M, Tov, N, Lishner, M, Elias, N, Piovaccari, G, De Pellegrin, A, Guardigli, G, Licciardello, G, Auguadro, C, Cuccia, C, Salvioni, A, Musumeci, G, Calabro, P, Novo, S, Faggiano, P, De Cesare, NB, Berti, S, Cavallini, C, Puccioni, E, Galvani, M, Tespili, M, Piatti, P, Palvarini, M, De Luca, G, Violini, R, De Leo, A, Filardi, PP, Ferratini, M, Ricca, V, Dai, K, Kamiya, H, Ando, K, Takeda, Y, Morino, Y, Hata, Y, Kimura, K, Kishi, K, Michishita, I, Uehara, H, Higashikata, T, Hirayama, A, Hirooka, K, Sakagami, S, Taguchi, S, Koike, A, Fujinaga, H, Koba, S, Kozuma, K, Kawasaki, T, Ono, Y, Shimizu, M, Katsuda, Y, Wada, A, Shinke, T, Kimura, T, Ako, J, Fujii, K, Takahashi, T, Sakamoto, T, Furukawa, Y, Sugino, H, Mano, T, Utsu, N, Ito, K, Haraguchi, T, Ueda, Y, Nishibe, A, Masutani, M, Fujimoto, K, Yoon, JH, Kim, SH, Park, HS, Chae, IH, Kim, MH, Jeong, MH, Rha, S, Kim, C, Hong, T, Tahk, SJ, Kim, Y, Busmane, A, Pontaga, N, Strelnieks, A, Mintale, I, Sime, I, Petrulioniene, Z, Kavaliauskiene, R, Jurgaitiene, R, Sakalyte, G, Slapikas, R, Norkiene, S, Misonis, N, Kibarskis, A, Kubilius, R, Bojovski, S, Kedev, S, Lozance, N, Kjovkaroski, A, Doncovska, S, Ong, TK, Kasim, S, Maskon, O, Kandasamy, B, Yusoff, K, Liew, HB, Mohamed, WMIW, Castillo, AG, Calvillo, JC, Campos, PF, Fragoso, JCN, Llamas, EAB, Gamba, MAA, Madrigal, JC, Salas, LGG, Rosas, EL, Diaz, BG, Vazquez, ES, Ackar, AN, Esperon, GAL, Sanchez, CRM, De Leon, MG, Otero, RS, Salmon, GF, Rios, JA, Ruiz, JAG, Breedveld, RW, Hoogslag, PAM, Suryapranata, H, Oomen, A, Wiersma, JJ, Van Der Wal, RMA, Van Huysduynen-Monraats, PSH, Karalis, I, Verdel, GJE, Brueren, BR, Troquay, RPT, Viergever, EP, Al-Windy, NYY, Bartels, GL, Cornel, JH, Hermans, WRM, Herrman, JPR, Bos, RJ, Groutars, RGEJ, Van Der Zwaan, CC, Kaplan, R, Ronner, E, Groenemeijer, BE, Bronzwaer, PNA, Liem, AAH, Rensing, BJWM, Bokern, MJJA, Nijmeijer, R, Hersbach, FMRJ, Willems, FF, Gosselink, ATM, Elliott, J, Wilkins, G, Fisher, R, Scott, D, Hart, H, Stewart, R, Harding, S, Ternouth, I, Fisher, N, Aitken, D, Anscombe, R, Davidson, L, Tomala, T, Nygard, O, Sparby, JA, Andersen, K, Gullestad, L, Jortveit, J, Munk, PS, Singsaas, EG, Halvorsen, S, Hurtig, U, Flores, RMC, Ticona, JRC, Velasquez, JRD, Miguel, SAN, Perez, ESS, Chambilla, JMC, Ayala, CAC, Leon, RPC, Gonzales, RJV, Zuniga, JDH, Cosavalente, LAC, Mannucci, JEB, Landeo, JH, Navarro, NCL, Concha, YMR, Chavez, VER, Hernandez, HAA, Nunez, CAZ, Ramos, WM, Ferrolino, A, Sy, RAG, Tirador, L, Sy, RG, Matiga, G, Coching, RM, Bernan, A, Rogelio, G, Morales, DD, Tan, E, Sulit, DJ, Wlodarczak, A, Jaworska, K, Skonieczny, G, Pawlowicz, L, Wojewod, P, Busz-Papiez, B, Bednarski, J, Goch, A, Staneta, P, Dulak, E, Budaj, A, Saminsk, K, Krasowski, W, Sudnik, W, Zurakowski, A, Skorski, M, Lysek, R, Miklaszewicz, B, Kubica, J, Lipko, JA, Kostarska-Srokosz, E, Piepiorka, M, Drzewiecka, A, Sciborski, R, Stasiewski, A, Blicharski, T, Bystryk, L, Szpajer, M, Korol, M, Czerski, T, Mirek-Bryniarska, E, Gniot, J, Lubinski, A, Gorny, J, Franek, E, Raczak, G, Szwed, H, Monteiro, P, Bastos, JM, Pereira, HH, Martins, D, Morais, J, Seixo, F, Mendonca, C, Botelho, A, Minescu, B, Istratoaie, O, Tesloianu, DN, Dorobantu, M, Cristian, G, Podoleanu, CGC, Constantinescu, MCA, Bengus, CM, Militaru, C, Rosu, D, Parepa, IR, Matei, AV, Alexandru, TM, Coman, I, Cioranu, RS, Dimulescu, D, Shvarts, Y, Orlikova, O, Kobalava, Z, Barbarash, OL, Markov, V, Lyamina, N, Gordienko, A, Zrazhevsky, K, Vishnevsky, AY, Gurevich, V, Stryuk, R, Lomakin, NV, Bokarev, I, Shalaev, S, Khaisheva, L, Chizhov, P, Viktorova, I, Osokina, N, Akatova, E, Chumakova, G, Libov, I, Voevoda, MI, Tretyakova, TV, Baranov, E, Shustov, S, Yakushin, S, Gordeev, I, Khasanov, N, Reshetko, O, Sotnikova, T, Molchanova, O, Nikolaev, K, Gapon, L, Baranova, E, Shogenov, Z, Kosmachova, E, Karpov, Y, Povzun, A, Egorova, L, Tyrenko, VV, Ivanov, IG, Kanorsky, S, Simic, D, Ivanovic, N, Davidovic, G, Tasic, N, Asanin, MR, Stojic, S, Apostolovic, SR, Ilic, S, Putnikovic, B, Stankovic, A, Arandjelovic, A, Radovanovic, S, Ristic, AD, Balinovac, J, Dincic, DV, Seferovic, P, Dodic, S, Dimkovic, S, Poh, KK, Ong, HY, Micko, K, Nociar, J, Pella, D, Fulop, P, Hranai, M, Palka, J, Mazur, J, Majercak, I, Dzupina, A, Fazekas, F, Gonsorcik, J, Bugan, V, Selecky, J, Kamensky, G, Strbova, J, Smik, R, Dukat, A, Olexa, P, Zuran, I, Poklukar, J, Suligoj, NC, Cevc, M, Cyster, HP, Ranjith, N, Corbett, C, Bayat, J, Makotoko, EM, Kapp, IE, Basson, MMD, Lottering, H, Van Zyl, LJ, Sebastian, PJ, Pillay, T, Saaiman, JA, Commerford, PJ, Cassimjee, S, Ebrahim, IO, Sarvan, M, Mynhardt, JH, Reuter, H, Moodley, R, Vida, M, Fillat, ARC, Peris, VB, Jimenez, FF, Marin, F, Fernandez, JMC, Gil-Extremera, B, Diz, FW, Garcia-Dorado, D, Iniguez, A, Fernandez, JT, Gonzalez-Juanatey, JR, Portales, JF, Murillo, FC, Pericas, LM, Zamorano, JL, Martin, MD, Cortada, JB, Martin, JJA, Fernandez, JRD, Fernandez, JFD, Lledo, JAG, Sales, JC, Rodriguez, JB, Tragant, GG, Benedicto, A, Gonzalez-Juanatey, C, Potau, MC, Perez, IP, De La Tassa, CM, Rincon, PLO, Recena, JB, Escudier, JM, Payeras, AC, Orcajo, NA, Valdivielso, P, Constantine, G, Haniffa, R, Tissera, N, Amarasekera, S, Fernando, N, Jayawardena, J, Santharaj, W, Ekanayaka, R, Mendis, S, Senaratne, V, Mayurathan, G, Sirisena, T, Rajapaksha, A, Herath, JI, Amarasena, N, Berglund, S, Rasmanis, G, Witt, N, Mourtzinis, G, Nicol, P, Hansen, O, Romeo, S, Jensen, SA, Torstensson, I, Ahremark, U, Sundelin, T, Moccetti, T, Muller, C, Mach, F, Binder, R, Tsai, WC, Ueng, KC, Lai, WT, Liu, ME, Hwang, JJ, Yin, WH, Hsieh, IC, Kuo, JY, Huang, TY, Fang, CY, Kaewsuwanna, P, Soonfuang, W, Jintapakorn, W, Sukonthasarn, A, Wongpraparut, N, Sastravaha, K, Sansanayudh, N, Kehasukcharoen, W, Piyayotai, D, Chotnoparatpat, P, Camsari, A, Kultursay, H, Mutlu, B, Ersanli, M, Demirtas, M, Kirma, C, Ural, E, Koldas, L, Karpenko, O, Prokhorov, A, Vakaluyk, I, Myshanych, H, Reshotko, D, Batushkin, V, Rudenko, L, Kovalskyi, I, Kushnir, M, Tseluyko, V, Mostovoy, Y, Stanislavchuk, M, Kyiak, Y, Karpenko, Y, Malynovsky, Y, Klantsa, A, Kutniy, O, Amosova, E, Tashchuk, V, Leshchuk, O, Rishko, M, Kopytsya, M, Yagensky, A, Vatutin, M, Bagriy, A, Barna, OM, Ushakov, O, Dzyak, G, Goloborodko, B, Rudenko, A, Zheleznyy, V, Trevelyan, J, Zaman, A, Lee, K, Moriarty, A, Aggarwal, RK, Clifford, P, Wong, YK, Iqbal, SM, Subkovas, E, Braganza, D, Sarkar, D, Storey, R, Griffiths, H, Mcclure, S, Muthusamy, R, Kurian, J, Levy, T, Barr, C, Kadr, H, Gerber, R, Simaitis, A, Soran, H, Mathur, A, Brodison, A, Oliver, R, Mudawi, T, Reynolds, T, Sharman, D, Butler, R, Wilkinson, P, Lip, GYH, Halcox, J, Vardi, G, Baldari, D, Brabham, D, Treasure, C, Dahl, C, Palmer, B, Wiseman, A, Puri, S, Mohart, AE, Ince, C, Flores, E, Wright, S, Cheng, SC, Rosenberg, M, Rogers, W, Kosinski, E, Forgosh, L, Waltman, J, Khan, M, Shoukfeh, M, Dagher, G, Lieber, I, Kumar, P, East, C, Krichmar, P, White, L, Knickelbine, T, Haldis, T, Gillespie, E, Suh, D, Arif, I, Akhter, F, Carlson, E, D'Urso, M, El-Ahdab, F, Nelson, W, Harris, B, Cohen, S, Carter, L, Sabatino, K, Haddad, T, Malik, A, Rao, S, Mulkay, A, Jovin, I, Klancke, K, Malhotra, V, Devarapalli, SK, Koren, M, Chandna, H, Dodds, G, Janik, M, Moran, J, Sumner, A, Kobayashi, J, Davis, W, Yazdani, S, Pasquini, J, Thakkar, M, Vedere, A, Leimbach, W, Rider, J, Singh, N, Shah, AV, Janosik, D, Pepine, C, Berman, B, Gelormini, J, Daniels, C, Keating, F, Kondo, NI, Shetty, S, Waider, W, Takata, T, Abu-Fadel, M, Shah, V, Aggarwal, R, Izzo, M, Kumar, A, Hattler, B, Link, C, Bortnick, A, Kinzfogl, G, Ghitis, A, Larry, J, Teufel, E, Kuhlman, P, Mclaurin, B, Zhang, WW, Thew, S, Abbas, J, White, M, Ranadive, N, Gring, C, Henderson, D, Schuchard, T, Farhat, N, Kline, G, Mahal, S, Whitaker, J, Speirs, S, Andersen, R, Daboul, N, Horwitz, P, Ponce, G, Jafar, Z, Mcgarvey, J, Panchal, V, Voyce, S, Blok, T, Sheldon, W, Azizad, MM, Schmalfuss, C, Picone, M, Herzog, W, Lindsey, J, Nowins, R, Lepor, N, El Shahawy, M, Weintraub, H, Irimpen, A, May, W, Galski, T, Chu, A, Mody, F, Hodes, Z, Rose, G, Fairlamb, J, Lambert, C, Raisinghani, A, Abbate, A, King, M, Carey, C, Gerber, J, Younis, L, Park, H, Vidovich, M, Knutson, T, Friedman, D, Chaleff, F, Loussararian, A, Rozeman, P, Kimmelstiel, C, Silver, K, Foster, M, Tonnessen, G, Amlani, M, Wali, A, Malozzi, C, Wattanakit, K, O'Donnell, PJ, Singal, D, Jaffrani, N, Banuru, S, Fisher, D, Xenakis, M, Perlmutter, N, Bhagwat, R, Strader, J, Akyea-Djamson, A, Labroo, A, Marais, HJ, Claxton, E, Berk, M, Rossi, P, Joshi, P, Khaira, AS, Kumkumian, G, Lupovitch, S, Purow, J, Welka, S, Hoffman, D, Fischer, S, Soroka, E, Eagerton, D, Pancholy, S, Ray, M, Farrar, M, Pollock, S, French, WJ, Diamantis, S, Gimple, L, Neustel, M, Schwartz, S, Pereira, E, Spriggs, D, Strain, J, Vo, A, Chane, M, Hall, J, Vijay, N, Lotun, K, Lester, FM, Nahhas, A, Pope, T, Nager, P, Vohra, R, Bashir, R, Ahmed, H, Berlowitz, M, Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, PS, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Lui, H, Keen, W, Westerhausen, D, Khurana, S, Agarwal, H, Birchem, J, Penny, W, Chang, M, Murphy, S, Schifferdecker, B, Gilbert, JM, Chalavarya, G, Eaton, C, Schmedtje, JF, Christenson, S, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Akright, L, Krawczyk, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, Camp, A, Lopes, R, Egydio, F, Kawakami, A, Oliveira, J, Wozniak, J, Matthews, A, Ratky, C, Valiris, J, Berdan, L, Hepditch, A, Quintero, K, Rorick, T, Westbrook, M, Pascual, A, Rovito, C, Bezault, M, Drouet, E, Simon, T, Alsweiler, C, Luyten, A, Aylward, P, Butters, J, Griffith, L, Shaw, M, Hagstrom, E, Grunberg, L, Islam, S, Bregeault, MF, Bougon, N, Faustino, D, Fontecave, S, Murphy, J, Tamby, JF, Verrier, M, Agnetti, V, Andersen, D, Badreddine, E, Bekkouche, M, Bouancheau, C, Brigui, I, Brocklehurst, M, Cianciarulo, J, Devaul, D, Domokos, S, Gache, C, Gobillot, C, Guillou, S, Healy, J, Heath, M, Jaiwal, G, Javierre, C, Labeirie, J, Monier, M, Morales, U, Mrabti, A, Mthombeni, B, Okan, B, Smith, L, Sheller, J, Sopena, S, Pellan, V, Benbernou, F, Bengrait, N, Lamoureux, M, Kralova, K, Scemama, M, Bejuit, R, Coulange, A, Berthou, C, Repincay, J, Lorenzato, C, Etienne, A, Gouet, V, Loizeau, V, Normand, M, Ourliac, A, Rondel, C, Adamo, A, Beltran, P, Barraud, P, Dubois-Gache, H, Halle, B, Metwally, L, Mourgues, M, Sotty, M, Vincendet, M, Cotruta, R, Zhu, CY, Fournie-Lloret, D, Morrello, C, Perthuis, A, Picault, P, Zobouyan, I, ODYSSEY OUTCOMES Comm Inve, Ege Üniversitesi, Cardiology, and Internal Medicine

Subjects
medicine.medical_specialty, Acute coronary syndrome, Time Factors, acute coronary syndrome, alirocumab, global burden of disease, hospitalization, myocardial infarction, PCSK9, 030204 cardiovascular system & hematology, Antibodies, Monoclonal, Humanized, Placebo, Patient Readmission, Risk Assessment, 03 medical and health sciences, Patient Admission, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Angina, Unstable, Hospital Mortality, 030212 general & internal medicine, Myocardial infarction, 03.02. Klinikai orvostan, Dyslipidemias, Alirocumab, Out of hospital, business.industry, Anticholesteremic Agents, Cholesterol, HDL, Cholesterol hdl, Cholesterol, LDL, medicine.disease, Treatment Outcome, Drug Therapy, Combination, Human medicine, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, business, Cardiovascular outcomes, Biomarkers
Abstract

Sherwood, Matthew/0000-0002-4305-5883; Abbate, Antonio/0000-0002-1930-785X; Moris, Cesar/0000-0002-2871-190X; Ersanli, Murat/0000-0003-1847-3087; Taskinen, Marja-Riitta/0000-0002-6229-3588; bastos, jose/0000-0002-9526-3123; Reshetko, Olga/0000-0003-3107-7636; Nikolaev, Konstantin/0000-0003-4601-6203; Leonardi, Sergio/0000-0002-4800-6132; Raffel, Owen C/0000-0001-5470-7050; Racca, Vittorio/0000-0002-4465-3789; Podoleanu, Cristian/0000-0001-9987-2519; Gislason, Gunnar H/0000-0002-0548-402X; Muenzel, Thomas/0000-0001-5503-4150; Tse, Hung Fat/0000-0002-9578-7808; Chumakova, Galina A/0000-0002-2810-6531, WOS: 000502609000004, PubMed: 31707826, Background: in ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab was compared with placebo, added to high-intensity or maximum tolerated statin treatment after acute coronary syndrome in 18924 patients. Alirocumab reduced first occurrence of the primary composite end point-coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or hospitalization for unstable angina-as well as total nonfatal cardiovascular events and all-cause deaths. the present analysis determined whether alirocumab reduced total (first and subsequent) hospitalizations and death and increased days alive and out of hospital (DAOH) and percent DAOH in ODYSSEY OUTCOMES. Methods and Results: in prespecified analyses, hazard functions for total hospitalizations and death were jointly estimated by a semiparametric model, while in post hoc analyses, DAOH and percent DAOH were compared between treatment groups with Poisson regression and one-inflated beta regression, respectively. With 16629 total hospitalizations and 726 deaths, 331 fewer hospitalizations, and 58 fewer deaths were observed with alirocumab compared with placebo, translating to 15.6 total hospitalizations or deaths avoided with alirocumab per 1000 patient-years of assigned treatment. Alirocumab reduced total hospitalizations (hazard ratio, 0.96 [95% CI, 0.92-1.00]; P=0.04) and increased DAOH relative to placebo (rate ratio, 1.003 [95% CI, 1.000-1.007]; P=0.05), primarily through a reduction in days dead (rate ratio, 0.847 [95% CI, 0.728-0.986]; P=0.03). Patients randomized to alirocumab were also more likely to survive to the end of the study without hospitalization (odds ratio, 1.06 [95% CI, 1.00-1.13]; P=0.03). Conclusions: Alirocumab reduced total hospitalizations with corresponding small increases in DAOH and percent DAOH. These outcomes provide alternative patient-centered metrics to capture the totality of alirocumab clinical efficacy after acute coronary syndrome. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01663402., Fondation Assistance Publique-Hopitaux de Paris, Paris, France, We thank the patients, study coordinators, and investigators who participated in this trial. Sophie Rushton-Smith, PhD (MedLink Healthcare Communications, London) provided editorial assistance in the preparation of the article (limited to editing for style, referencing, and figure and table editing) and was funded by Fondation Assistance Publique-Hopitaux de Paris, Paris, France.

Published
2019

9. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome

Author

Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, Edelberg JM, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Lecorps G, Mahaffey KW, Moryusef A, Pordy R, Quintero K, Roe MT, Sasiela WJ, Tamby JF, Tricoci P, White HD, Zeiher AM, and ODYSSEY OUTCOMES Committees and Investigators

Published
2018

10. Use of High-Intensity Statin Therapy Post-Acute Coronary Syndrome in the Ongoing ODYSSEY OUTCOMES Trial of Alirocumab, A Proprotein Convertase Subtilisin/Kexin type 9 Monoclonal Antibody, Versus Placebo: Interim Baseline Data

Author

White, H., primary, Goodman, S., additional, Schwartz, G., additional, Bhatt, D., additional, Bittner, V., additional, Diaz, R., additional, Hanotin, C., additional, Harrington, R., additional, Jukema, J., additional, Moryusef, A., additional, Pordy, R., additional, Roe, M., additional, Sasiela, W., additional, Szarek, M., additional, Tamby, J., additional, Zeiher, A., additional, and Steg, P., additional

Published
2017
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17. Viscoelasticity of vibrated granular suspensions.

Author

Hanotin, C., de Richter, S. Kiesgen, Michot, L. J., and Marchal, Ph.

Subjects
*VISCOELASTICITY, *SUSPENSIONS (Chemistry), *RHEOLOGY, *PREDICTION models, *STRAINS & stresses (Mechanics)
Abstract

We propose, in this paper, a model for predicting the rheological response of both vibrated and sheared 3D granular suspensions in stationary and nonstationary conditions. The major assumption of this model is the inherent bimodal behavior of chain forces in granular packings. The model is set up from a kinetic equation describing the dynamic exchange between a population of strongly correlated caged particles and a population of slightly correlated free particles. To compare the predictions of the model to experimental results, the kinetic equation is transformed into a differential constitutive equation, relating stress to strain, by including the effect of the interstitial fluid on the suspension. With only four adjustable parameters intrinsic to the system (i.e., independent of the type of rheological test used), the model is in very close agreement with experiments. Despite the fact that our approach remains at a mean-field level, it is able to predict and describe several rheological behaviors, in stationary, nonstationary conditions, linear and nonlinear regimes, including Newtonian and frictional Coulombian regimes, as well as elastic Hookean and viscoelastic Maxwellian behaviors. It then appears that this two-state approach allows capturing both the viscoelastic behavior of dry granular materials and granular suspensions. Vibrated dense suspensions and granular media are thus unified under a common framework. [ABSTRACT FROM AUTHOR]

Published
2015
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20. Two-state model to describe the rheological behavior of vibrated granular matter.

Author

Marchail, Ph., Hanotin, C., Michot, L. J., and de Richter, S. Kiesgen

Subjects
*RHEOLOGY, *VIBRATION (Mechanics), *GRANULAR materials, *PREDICTION models, *DYNAMICAL systems, *HERTZIAN contacts
Abstract

In this paper, we present a model aimed at predicting the rheological response of a 3D dry granular system to nonstationary mechanical solicitations, subjected or not to vibrations. This model is based on a phenomenological two-state approach related to the inherent bimodal behavior of chain forces in granular packing. It is set up from a kinetic equation describing the dynamics of the contact network. To allow experimental assessment, the kinetic equation is transformed into a differential constitutive equation, relating stress to strain, from which rheological properties can be derived. Its integration allows predicting and describing several rheological behaviors, in stationary and nonstationary conditions, including viscous (Newtonian) and frictional (Coulombian) regimes, as well as elastic linear (Hookean and Maxwellian) and nonlinear behaviors. Despite its simplicity, since it involves only three independent parameters, the model is in very close agreement with experiments. Moreover, within experimental errors, the values of these parameters are independent of the type of test used to determine them, evidence of the self-consistency of the model. [ABSTRACT FROM AUTHOR]

Published
2013
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21. Efficacy of Rimonabant in Obese Patients with Binge Eating Disorder.

Author

Pataky, Z., Gasteyger, C., Ziegler, O., Rissanen, A., Hanotin, C., and Golay, A.

Subjects
ANTIOBESITY agents, RIMONABANT, PLACEBOS, BULIMIA, OVERWEIGHT women, TREATMENT effectiveness, PATIENTS, THERAPEUTICS
Abstract

In obesity, a dysregulation of the endocannabinoid system has been shown. The endocannabinoid receptor blockage by rimonabant demonstrated interesting metabolic effects. However, the role of rimonabant in weight loss of patients with binge eating disorder has not been investigated. Thus, our aim was to evaluate the effects of rimonabant on body weight in obese patients with binge eating disorders. This multicenter, randomized, double-blind, placebo- controlled study included 289 obese subjects (age 18-70 years, body mass index 30-45 kg/ m² ) with binge eating disorders. Subjects were randomized (1:1) to receive rimonabant 20 mg/ day or placebo for 6 months. In total, 289 participants (age: 43.2 ± 10.5 yrs, 91 % of women) were randomized. The completer rate was similar (71 %) in both treatment and placebo groups. Participants treated with rimonabant lost 4.7 ± 5.2 % of their initial body weight, vs. 0.4 ± 4.5 % in the placebo group (difference between both groups: 4.4 ± 0.6 kg, p < 0.0001). The rimonabant group showed a greater reduction on the binge eating scale total score (mean ± SD - 40.9 ± 35.2 %) vs. placebo ( - 29.9 ± 34.6 %, p = 0.02). The incidence of treatment emergent adverse events was comparable in both the rimonabant (82.5 %) and placebo (76.0 %) group. Discontinuations due to treatment emergent adverse events occurred in 13.3 % rimonabant-treated vs. 6.2 % placebo-treated participants. In conclusion, this is the only randomised, placebo- controlled, double-blind trial having assessed the effect of rimonabant in patients with binge eating disorders. The rimonabant treatment reduced body weight significantly more than placebo in obese subjects with binge eating. [ABSTRACT FROM AUTHOR]

Published
2013
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22. Efficacy and tolerability of sibutramine in obese patients: a dose-ranging study.

Author

Hanotin, C, Thomas, F, Jones, S P, Leutenegger, E, and Drouin, P

Subjects
*SEROTONIN uptake inhibitors, *ADRENALINE, *ANTIOBESITY agents
Abstract

OBJECTIVES: To assess the weight-reducing effects and tolerability of 5 mg, 10 mg and 15 mg daily doses of sibutramine, a novel serotonin and noradrenaline reuptake inhibitor (SNRI). DESIGN: Multicentre, double-blind, and placebo-controlled study. After a one week run-in period, patients were randomized to receive placebo or sibutramine over a 12-week period. Advice on diet and behaviour modification was provided. One follow-up was conducted four weeks after cessation of treatment. SUBJECTS: 235 obese outpatients, aged 18–65 y with a body mass index (BMI) within the range 27–40 kg/m. MEASUREMENTS: Weight, height, waist and hip circumference, and medical history, assessment of hunger, satiety, appetite and craving for sweet, savoury and carbohydrate foods, and also for carbohydrate snacking, standard laboratory assessments, blood pressure, heart rate and ECG. RESULTS: The group mean (±s.e.m.) weight loss at end-point was 1.4±0.5 kg for placebo (n=59), 2.4±0.5 kg for 5 mg sibutramine (n=56), 5.1±0.5 kg for 10 mg sibutramine (n=59) and 4.9±0.5 kg (n=62) for 15 mg sibutramine. The difference observed between the placebo and the 10 mg and 15 mg groups was statistically significant from week 2 onwards (P<0.01), but there was no significant difference between these sibutramine groups. The percentage of patients losing >5% of initial bodyweight was significantly greater for 15 mg sibutramine (55%) and 10 mg sibutramine (49%) than for treatment with placebo (19%), (P<0.001). During the double-blind period, 41 patients (17%) withdrew prematurely and 168 patients (71%) reported 453 adverse events. The incidence and type of adverse event and the rates of withdrawal, were not significantly different in the four groups. No significant differences between the groups were observed, in respect of changes in systolic and diastolic blood pressure, but a significant increase in heart rate (about 4 beats/min) was noted for patients who... [ABSTRACT FROM AUTHOR]

Published
1998
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24. Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial

Author

Kausik K Ray, Helen M Colhoun, Michael Szarek, Marie Baccara-Dinet, Deepak L Bhatt, Vera A Bittner, Andrzej J Budaj, Rafael Diaz, Shaun G Goodman, Corinne Hanotin, Robert A Harrington, J Wouter Jukema, Virginie Loizeau, Renato D Lopes, Angèle Moryusef, Jan Murin, Robert Pordy, Arsen D Ristic, Matthew T Roe, José Tuñón, Harvey D White, Andreas M Zeiher, Gregory G Schwartz, Philippe Gabriel Steg, Gregory G. Schwartz, Ph. Gabriel Steg, Deepak L. Bhatt, Vera A. Bittner, Shaun G. Goodman, Robert A. Harrington, J. Wouter Jukema, Harvey D. White, Andreas M. Zeiher, Pierluigi Tricoci, Matthew T. Roe, Kenneth W. Mahaffey, Jay M. Edelberg, Guillaume Lecorps, William J. Sasiela, Jean-François Tamby, Philip E. Aylward, Heinz Drexel, Peter Sinnaeve, Mirza Dilic, Renato D. Lopes, Nina N. Gotcheva, Juan-Carlos Prieto, Huo Yong, Patricio López-Jaramillo, Ivan Pećin, Zeljko Reiner, Petr Ostadal, Margus Viigimaa, Markku S. Nieminen, Vakhtang Chumburidze, Nikolaus Marx, Nicolas Danchin, Evangelos Liberopoulos, Pablo Carlos Montenegro Valdovinos, Hung-Fat Tse, Robert Gabor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo Soo Kim, Sang-Hyun Kim, Andrejs Erglis, Aleksandras Laucevicius, Sasko Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, Marco Alings, Sigrun Halvorsen, Roger M. Correa Flores, Andrzej Budaj, Joao Morais, Maria Dorobantu, Yuri Karpov, Arsen D. Ristic, Terrance Chua, Zlatko Fras, Anthony J. Dalby, H. Asita de Silva, Emil Hagström, Ulf Landmesser, Chern-En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K. Ray, Patrick M. Moriarty, Robert Vogel, Bernard Chaitman, Sheryl F. Kelsey, Anders G. Olsson, Jean-Lucien Rouleau, Maarten L. Simoons, Karen Alexander, Chiara Meloni, Robert Rosenson, Eric J.G. Sijbrands, John H. Alexander, Luciana Armaganijan, Akshay Bagai, Maria Cecilia Bahit, J. Matthew Brennan, Shaun Clifton, Adam D. DeVore, Shalonda Deloatch, Sheila Dickey, Keith Dombrowski, Grégory Ducrocq, Zubin Eapen, Patricia Endsley, Arleen Eppinger, Robert W. Harrison, Connie Ng Hess, Mark A. Hlatky, Joseph Dedrick Jordan, Joshua W. Knowles, Bradley J. Kolls, David F. Kong, Sergio Leonardi, Linda Lillis, David J. Maron, Jill Marcus, Robin Mathews, Rajendra H. Mehta, Robert J. Mentz, Humberto Graner Moreira, Chetan B. Patel, Sabrina Bernardez-Pereira, Lynn Perkins, Thomas J. Povsic, Etienne Puymirat, William Schuyler Jones, Bimal R. Shah, Matthew W. Sherwood, Kenya Stringfellow, Darin Sujjavanich, Mustafa Toma, Charlene Trotter, Sean Van Diepen, Matthew D. Wilson, Andrew T. Yan, Lilia B. Schiavi, Marcelo Garrido, Andrés F. Alvarisqueta, Sonia A. Sassone, Anselmo P. Bordonava, Alberto E. Alves De Lima, Jorge M. Schmidberg, Ernesto A. Duronto, Orlando C. Caruso, Leonardo P. Novaretto, Miguel Angel Hominal, Oscar R. Montaña, Alberto Caccavo, Oscar A. Gomez Vilamajo, Alberto J. Lorenzatti, Luis R. Cartasegna, Gustavo A. Paterlini, Ignacio J. Mackinnon, Guillermo D. Caime, Marcos Amuchastegui, Oscar Salomone, Oscar R. Codutti, Horacio O. Jure, Julio OE Bono, Adrian D. Hrabar, Julio A. Vallejos, Rodolfo A. Ahuad Guerrero, Federico Novoa, Cristian A. Patocchi, Cesar J. Zaidman, Maria E. Giuliano, Ricardo D. Dran, Marisa L. Vico, Gabriela S. Carnero, Pablo N. Guzman, Juan C. Medrano Allende, Daniela F. Garcia Brasca, Miguel H Bustamante Labarta, Sebastian Nani, Eduardo DS Blumberg, Hugo R Colombo, Alberto Liberman, Victorino Fuentealba, Hector L Luciardi, Gabriel D Waisman, Mario A Berli, Ruben O Garcia Duran, Horacio G Cestari, Hugo A Luquez, Jorge A Giordano, Silvia S Saavedra, Gerardo Zapata, Osvaldo Costamagna, Susana Llois, Jonathon H Waites, Nicholas Collins, Allan Soward, Chris LS Hii, James Shaw, Margaret A Arstall, John Horowitz, Daniel Ninio, James F Rogers, David Colquhoun, Romulo E Oqueli Flores, Philip Roberts-Thomson, Owen Raffel, Sam J Lehman, Constantine Aroney, Steven GM Coverdale, Paul J Garrahy, Gregory Starmer, Mark Sader, Patrick A Carroll, Ronald Dick, Robert Zweiker, Uta Hoppe, Kurt Huber, Rudolf Berger, Georg Delle-Karth, Bernhard Frey, Franz Weidinger, Dirk Faes, Kurt Hermans, Bruno Pirenne, Attilio Leone, Etienne Hoffer, Mathias CM Vrolix, Luc De Wolf, Bart Wollaert, Marc Castadot, Karl Dujardin, Christophe Beauloye, Geert Vervoort, Harry Striekwold, Carl Convens, John Roosen, Emanuele Barbato, Marc Claeys, Frank Cools, Ibrahim Terzic, Fahir Barakovic, Zlatko Midzic, Belma Pojskic, Emir Fazlibegovic, Mehmed Kulić, Azra Durak-Nalbantic, Dusko Vulic, Adis Muslibegovic, Boris Goronja, Gilmar Reis, Luciano Sousa, Jose C Nicolau, Flavio E Giorgeto, Ricardo P Silva, Lilia Nigro Maia, Rafael Rech, Paulo RF Rossi, Maria José AG Cerqueira, Norberto Duda, Renato Kalil, Adrian Kormann, José Antonio M Abrantes, Pedro Pimentel Filho, Ana Priscila Soggia, Mayler ON de Santos, Fernando Neuenschwander, Luiz C Bodanese, Yorghos L Michalaros, Freddy G Eliaschewitz, Maria H Vidotti, Paulo E Leaes, Roberto V Botelho, Sergio Kaiser, Euler Roberto Fernandes Manenti, Dalton B Precoma, Jose C Moura Jorge, Pedro G de B Silva, Jose A Silveira, Wladmir Saporito, Jose A Marin-Neto, Gilson S Feitosa, Luiz Eduardo F Ritt, Juliana A de Souza, Fernando Costa, Weimar KSB Souza, Helder JL Reis, Leandro Machado, José Carlos Aidar Ayoub, Georgi V Todorov, Fedya P Nikolov, Elena S Velcheva, Maria L Tzekova, Haralambi O Benov, Stanislav L Petranov, Haralin S Tumbev, Nina S Shehova-Yankova, Dimitar T Markov, Dimitar H Raev, Mihail N Mollov, Kostadin N Kichukov, Katya A Ilieva-Pandeva, Raya Ivanova, Maryana Gospodinov, Valentina M Mincheva, Petar V Lazov, Bojidar I Dimov, Manohara Senaratne, James Stone, Jan Kornder, Stephen Pearce, Danielle Dion, Daniel Savard, Yves Pesant, Amritanshu Pandey, Simon Robinson, Gilbert Gosselin, Saul Vizel, Gordon Hoag, Ronald Bourgeois, Anne Morisset, Eric Sabbah, Bruce Sussex, Simon Kouz, Paul MacDonald, Ariel Diaz, Nicolas Michaud, David Fell, Raymond Leung, Tycho Vuurmans, Christopher Lai, Frank Nigro, Richard Davies, Gustavo Nogareda, Ram Vijayaraghavan, John Ducas, Serge Lepage, Shamir Mehta, James Cha, Robert Dupuis, Peter Fong, Sohrab Lutchmedial, Josep Rodes-Cabau, Hussein Fadlallah, David Cleveland, Thao Huynh, Iqbal Bata, Adnan Hameed, Cristian Pincetti, Sergio Potthoff, Juan C Prieto, Monica Acevedo, Arnoldo Aguirre, Margarita Vejar, Mario Yañez, Guillermo Araneda, Mauricio Fernandez, Luis Perez, Paola Varleta, Fernando Florenzano, Laura Huidobro, Carlos A Raffo, Claudia Olivares, Leonardo Nahuelpan, Humberto Montecinos, Jiyan Chen, Yugang Dong, Weijian Huang, Jianzhong Wang, Shi'An Huang, Zhuhua Yao, Xiang Li, Lan Cui, Wenhua Lin, Yuemin Sun, Jingfeng Wang, Jianping Li, Xuelian Zhang, Hong Zhu, Dandan Chen, Lan Huang, Shaohong Dong, Guohai Su, Biao Xu, Xi Su, Xiaoshu Cheng, Jinxiu Lin, Wenxia Zong, Huanming Li, Yi Feng, Dingli Xu, Xinchun Yang, Yuannan Ke, Xuefeng Lin, Zheng Zhang, Zeqi Zheng, Zhurong Luo, Yundai Chen, Chunhua Ding, Yi Zhong, Yang Zheng, Xiaodong Li, Daoquan Peng, Shuiping Zhao, Ying Li, Xuebo Liu, Meng Wei, Shaowen Liu, Yihua Yu, Baiming Qu, Weihong Jiang, Yujie Zhou, Xingsheng Zhao, Zuyi Yuan, Ying Guo, Xiping Xu, Xubo Shi, Junbo Ge, Guosheng Fu, Feng Bai, Weiyi Fang, Xiling Shou, Xiangjun Yang, Jian'An Wang, Meixiang Xiang, Yingxian Sun, Qinghua Lu, Ruiyan Zhang, Jianhua Zhu, Yizhou Xu, Zhongcai Fan, Tianchang Li, Chun Wu, Nicolas Jaramillo, Gregorio Sanchez Vallejo, Diana C Luna Botia, Rodrigo Botero Lopez, Dora I Molina De Salazar, Alberto J Cadena Bonfanti, Carlos Cotes Aroca, Juan Diego Higuera, Marco Blanquicett, Sandra I Barrera Silva, Henry J Garcia Lozada, Julian A Coronel Arroyo, Jose L Accini Mendoza, Ricardo L Fernandez Ruiz, Alvaro M. Quintero Ossa, Fernando G Manzur Jatin, Aristides Sotomayor Herazo, Jeffrey Castellanos Parada, Rafael Suarez Arambula, Miguel A Urina Triana, Angela M Fernandez Trujillo, Maja Strozzi, Siniša Car, Melita Jerić, Davor Miličić, Martina Lovrić Benčić, Hrvoje Pintarić, Đeiti Prvulović, Jozica Šikić, Viktor Peršić, Dean Mileta, Kresimir Štambuk, Zdravko Babić, Vjekoslav Tomulic, Josip Lukenda, Stanka Mejic-Krstulovic, Boris Starcevic, Jindrich Spinar, David Horak, Zdenek Velicka, Josef Stasek, David Alan, Vilma Machova, Ales Linhart, Vojtech Novotny, Vladimir Kaucak, Richard Rokyta, Robert Naplava, Zdenek Coufal, Vera Adamkova, Ivo Podpera, Jiri Zizka, Zuzana Motovska, Ivana Marusincova, Premysl Svab, Petr Heinc, Jiri Kuchar, Petr Povolny, Jiri Matuska, Steen H Poulsen, Bent Raungaard, Peter Clemmensen, Lia E Bang, Ole May, Morten Bøttcher, Jens D Hove, Lars Frost, Gunnar Gislason, John Larsen, Peter Betton Johansen, Flemming Hald, Peter Johansen, Jørgen Jeppesen, Tonny Nielsen, Kjeld S Kristensen, Piotr Maria Walichiewicz, Jens D Lomholdt, Ib C Klausen, Peter Kaiser Nielsen, Flemming Davidsen, Lars Videbaek, Mai Soots, Veiko Vahula, Anu Hedman, Üllar Soopõld, Kaja Märtsin, Tiina Jurgenson, Arved Kristjan, Juhani K Helsinki, Saila Vikman, Heikki Huikuri, Juhani Airaksinen, Pierre Coste, Emile Ferrari, Olivier Morel, Gilles Montalescot, Jacques Machecourt, Gilles Barone-Rochette, Jacques Mansourati, Yves Cottin, Florence Leclercq, Abdelkader Belhassane, Nicolas Delarche, Franck Boccara, Franck Paganelli, Jérôme Clerc, Francois Schiele, Victor Aboyans, Vincent Probst, Jacques Berland, Thierry Lefèvre, Bernard Citron, Irakli Khintibidze, Tamaz Shaburishvili, Zurab Pagava, Ramaz Ghlonti, Zaza Lominadze, George Khabeishvili, Rayyan Hemetsberger, Kemala Edward, Ursula Rauch-Kröhnert, Matthias Stratmann, Karl-Friedrich Appel, Ekkehard Schmidt, Heyder Omran, Christoph Stellbrink, Thomas Dorsel, Emmanouil Lianopoulos, Hans Friedrich Vöhringer, Roger Marx, Andreas Zirlik, Detlev Schellenberg, Thomas Heitzer, Ulrich Laufs, Christian Werner, Stephan Gielen, Sebastian Nuding, Bernhard Winkelmann, Steffen Behrens, Karsten Sydow, Mahir Karakas, Gregor Simonis, Thomas Muenzel, Nikos Werner, Stefan Leggewie, Dirk Böcker, Rüdiger Braun-Dullaeus, Nicole Toursarkissian, Michael Jeserich, Matthias Weißbrodt, Tim Schaeufele, Joachim Weil, Heinz Völler, Johannes Waltenberger, Mohammed Natour, Susanne Schmitt, Dirk Müller-Wieland, Stephan Steiner, Lothar Heidenreich, Elmar Offers, Uwe Gremmler, Holger Killat, Werner Rieker, Sotiris Patsilinakos, Athanasios Kartalis, Athanassios Manolis, Dimitrios Sionis, Geargios Chachalis, Ioannis Skoumas, Vasilios Athyros, Panagiotis Vardas, Frangkiskos Parthenakis, Dimitrios Alexopoulos, Georgios Hahalis, John Lekakis, Apostolos Hatzitolios, Sergio R Fausto Ovando, Juan L Arango Benecke, Edgar R Rodriguez De Leon, Bryan PY Yan, David CW Siu, Tibor Turi, Bela Merkely, Imre Ungi, Geza Lupkovics, Lajos Nagy, András Katona, István Édes, Gábor Müller, Iván Horvath, Tibor Kapin, Zsolt Szigeti, József Faluközy, Mukund Kumbla, Manjinder Sandhu, Sharath Annam, Naveen Reddy Proddutur, Reddy Regella, Rajendra K Premchand, Ajaykumar Mahajan, Sudhir Pawar, Atul D Abhyanakar, Prafulla Kerkar, Ravishankar A Govinda, Abraham Oomman, Dhurjati Sinha, Sachin N Patil, Dhiman Kahali, Jitendra Sawhney, Abhijeet B Joshi, Sanjeev Chaudhary, Pankaj Harkut, Santanu Guha, Sanjay Porwal, Srimannarayana Jujjuru, Ramesh B Pothineni, Minguel R Monteiro, Aziz Khan, Shamanna S Iyengar, Jasprakash Singh Grewal, Manoj Chopda, Mahesh C Fulwani, Aparna Patange, Patil Sachin, Vijay K Chopra, Naresh K Goyal, Rituparna Shinde, Gajendra V Manakshe, Nitin Patki, Sumeet Sethi, Vengatesh Munusamy, Sunil Karna, Sunil Thanvi, Srilakshmi Adhyapak, Chandrakant Patil, Ulhas Pandurangi, Rishabh Mathur, Jugal Gupta, Suhas Kalashetti, Ajit Bhagwat, Bagirath Raghuraman, Shiv Kumar Yerra, Prasant Bhansali, Rohidas Borse, Patil Rahul, Srihari Das, Vinay Kumar, Jabir Abdullakutty, Shireesh Saathe, Priya Palimkar, Shireesh Sathe, Shaul Atar, Michael Shechter, Morris Mosseri, Yaron Arbel, Chorin Ehud, Havakuk Ofer, Chaim Lotan, Uri Rosenschein, Amos Katz, Yaakov Henkin, Adi Francis, Marc Klutstein, Eugenia Nikolsky, Robert Zukermann, Yoav Turgeman, Majdi Halabi, Alon Marmor, Ran Kornowski, Michael Jonas, Offer Amir, Yonathan Hasin, Yoseph Rozenman, Shmuel Fuchs, Vered Zvi, Osamah Hussein, Dov Gavish, Zvi Vered, Yoseph Caraco, Mazen Elias, Naveh Tov, Efrat Wolfovitz, Michael Lishner, Nizar Elias, Giancarlo Piovaccari, Annamaria De Pellegrin, Raffaella Garbelotto, Gabriele Guardigli, Valgimigli Marco, Giovanni Licciardello, Carla Auguadro, Filippo Scalise, Claudio Cuccia, Alessandro Salvioni, Giuseppe Musumeci, Michelle Senni, Paolo Calabrò, Salvatore Novo, Pompilio Faggiano, Marco Metra, Nicoletta B De Cesare, Sergio Berti, Claudio Cavallini, Enrico Puccioni, Marcello Galvani, Maurizio Tespili, Piermarco Piatti, Michela Palvarini, Giuseppe De Luca, Roberto Violini, Alessandro De Leo, Zoran Olivari, Pasquale Perrone Filardi, Maurizio Ferratini, Vittorio Racca, Kazuoki Dai, Yuji Shimatani, Haruo Kamiya, Kenji Ando, Yoshihiro Takeda, Yoshihiro Morino, Yoshiki Hata, Kazuo Kimura, Koichi Kishi, Ichiro Michishita, Hiroki Uehara, Toshinori Higashikata, Atsushi Hirayama, Keiji Hirooka, Yasuji Doi, Satoru Sakagami, Shuichi Taguchi, Akihiro Koike, Hiroyuki Fujinaga, Shinji Koba, Ken Kozuma, Tomohiro Kawasaki, Yujiro Ono, Masatoshi Shimizu, Yousuke Katsuda, Atsuyuki Wada, Toshiro Shinke, Junya Ako, Kenshi Fujii, Toshiyuki Takahashi, Tomohiro Sakamoto, Koichi Nakao, Yutaka Furukawa, Hiroshi Sugino, Ritsu Tamura, Toshiaki Mano, Masaaki Uematsu, Noriaki Utsu, Kashima Ito, Takuya Haraguchi, Katsuhiko Sato, Yasunori Ueda, Akira Nishibe, Kazuteru Fujimoto, Motomaru Masutani, Jung Han Yoon, Hack-Lyoung Kim, Hun Sik Park, In-Ho Chae, Moo Hyun Kim, Myung Ho Jeong, Seungwoon Rha, Chongjin Kim, Hyo-Soo Kim, Hae Young Kim, Taekjong Hong, Seung-Jea Tahk, Youngkwon Kim, Arija Busmane, Natalija Pontaga, Aldis Strelnieks, Iveta Mintale, Iveta Sime, Zaneta Petrulioniene, Roma Kavaliauskiene, Ruta Jurgaitiene, Gintare Sakalyte, Rimvydas Slapikas, Sigute Norkiene, Nerijus Misonis, Aleksandras Kibarskis, Raimondas Kubilius, Stojko Bojovski, Nensi Lozance, Aleksandar Kjovkaroski, Snezana Doncovska, Tiong Kiam Ong, Sazzli Kasim, Oteh Maskon, Balachandran Kandasamy, Houng B Liew, Wan Mohd Izani Wan Mohamed, Armando García Castillo, Jorge Carrillo Calvillo, Pedro Fajardo Campos, Juan Carlos Núñez Fragoso, Edmundo Alfredo Bayram Llamas, Marco Antonio Alcocer Gamba, Jaime Carranza Madrigal, Luis Gerardo González Salas, Enrique López Rosas, Belinda González Díaz, Eduardo Salcido Vázquez, Alfredo Nacoud Ackar, Guillermo Antonio Llamas Esperón, Carlos Rodolfo Martínez Sánchez, María Guerrero De Leon, Rodrigo Suarez Otero, Guillermo Fanghänel Salmón, Jesús Antonio Pérez Ríos, José Angel Garza Ruíz, Robert W Breedveld, Margriet Feenema-Aardema, Alida Borger-Van Der Burg, Pieter AM Hoogslag, Harry Suryapranata, Antonius Oomen, Paulus Van Haelst, Jacobijne J Wiersma, Dirk Basart, Ruud MA Van Der Wal, Peter Zwart, Pascalle Monraats, Henricus Van Kesteren, Ioannis Karalis, Johan Jukema, Gerardus JE Verdel, Bart RG Brueren, Roland PTh Troquay, Eric P Viergever, Nadea YY Al-Windy, Gerard L Bartels, Jan H Cornel, Walter RM Hermans, Johannes PR Herrman, Robert J Bos, Reginald GEJ Groutars, Coenraad C Van Der Zwaan, Refik Kaplan, Raymond Lionarons, Eelko Ronner, Bjorn E Groenemeijer, Patrick NA Bronzwaer, Anho AH Liem, Bernard JWM Rensing, Marcel JJA Bokern, Remco Nijmeijer, Ferry MRJ Hersbach, Frank F Willems, Antonius TM Gosselink, Saman Rasoul, John Elliott, Gerard Wilkins, Raewyn Fisher, Douglas Scott, Hamish Hart, Ralph Stewart, Scott Harding, Ian Ternouth, Nicholas Fisher, Samuel Wilson, Denise Aitken, Russell Anscombe, Laura Davidson, Tadeusz Tomala, Ottar Nygård, Jon Arne Sparby, Kjell Andersen, Lars Gullestad, Jarle Jortveit, Peter S Munk, Erlend gyllensten Singsaas, Ulf Hurtig, Jorge R Calderon Ticona, Julio R Durand Velasquez, Sandra A Negron Miguel, Enrique S Sanabria Perez, Jesus M Carrion Chambilla, Carlos A Chavez Ayala, Reynaldo P Castillo Leon, Rolando J Vargas Gonzales, Jose D Hernandez Zuniga, Luis A Camacho Cosavalente, Jorge E Bravo Mannucci, Javier Heredia Landeo, Nassip C Llerena Navarro, Yudy M Roldan Concha, Víctor E Rodriguez Chavez, Henry A Anchante Hernandez, Carlos A Zea Nunez, Walter Mogrovejo Ramos, Arthur Ferrolino, Rosa Allyn G Sy, Louie Tirador, Rody G Sy, Generoso Matiga, Raul Martin Coching, Alisa Bernan, Gregorio Rogelio, Dante D. Morales, Edgar Tan, Dennis Jose Sulit, Adrian Wlodarczak, Krystyna Jaworska, Grzegorz Skonieczny, Lidia Pawlowicz, Pawel Wojewoda, Benita Busz-Papiez, Janusz Bednarski, Aleksander Goch, Pawel Staneta, Elzbieta Dulak, Krzysztof Saminski, Wlodzimierz Krasowski, Wanda Sudnik, Aleksander Zurakowski, Marcin Skorski, Beata Miklaszewicz, Jacek Kubica, Jan Andrzej Lipko, Edyta Kostarska-Srokosz, Marek Piepiorka, Anna Drzewiecka, Arkadiusz Stasiewski, Tomasz Blicharski, Leszek Bystryk, Michal Szpajer, Marek Korol, Tomasz Czerski, Ewa Mirek-Bryniarska, Jacek Gniot, Andrzej Lubinski, Jerzy Gorny, Edward Franek, Grzegorz Raczak, Hanna Szwed, Pedro Monteiro, Jose Mesquita Bastos, Helder H Pereira, Dinis Martins, Filipe Seixo, Carlos Mendonça, Ana Botelho, Francisca Caetano, Bogdan Minescu, Octavian Istratoaie, Dan N Tesloianu, Gabriel Cristian, Silviu Dumitrescu, Cristian GC Podoleanu, Mircea CA Constantinescu, Cristina M Bengus, Constantin Militaru, Doina Rosu, Irinel R Parepa, Adrian V Matei, Tom M Alexandru, Mihaela Malis, Ioan Coman, Rodica Stanescu-Cioranu, Doina Dimulescu, Yury Shvarts, Olga Orlikova, Zhanna Kobalava, Olga L Barbarash, Valentin Markov, Nadezhda Lyamina, Alexander Gordienko, Konstantin Zrazhevsky, Alexander Y Vishnevsky, Victor Gurevich, Raisa Stryuk, Nikita V Lomakin, Igor Bokarev, Tatiana Khlevchuk, Sergey Shalaev, Larisa Khaisheva, Petr Chizhov, Inna Viktorova, Natalya Osokina, Vladimir Shchekotov, Evgenia Akatova, Galina Chumakova, Igor Libov, Mikhail I Voevoda, Tatyana V Tretyakova, Evgeny Baranov, Sergey Shustov, Sergey Yakushin, Ivan Gordeev, Niiaz Khasanov, Olga Reshetko, Tatiana Sotnikova, Olga Molchanova, Konstantin Nikolaev, Liudmila Gapon, Elena Baranova, Zaur Shogenov, Elena Kosmachova, Yuriy Karpov, Anton Povzun, Liudmila Egorova, Vadim V Tyrenko, Igor G Ivanov, Masterov Ilya, Sergey Kanorsky, Dragan Simic, Nikola Ivanovic, Goran Davidovic, Nebojsa Tasic, Milika R. Asanin, Stevo Stojic, Svetlana R. Apostolovic, Stevan Ilic, Biljana Putnikovic Tosic, Aleksandar Stankovic, Aleksandra Arandjelovic, Slavica Radovanovic, Branislava Todic, Jovan Balinovac, Dragan V. Dincic, Petar Seferovic, Ana Karadzic, Slobodan Dodic, Sinisa Dimkovic, Tamara Jakimov, Kian-Keong Poh, Hean Yee Ong, Justin Tang I-Shing, Karol Micko, Jan Nociar, Daniel Pella, Peter Fulop, Marian Hranai, Juraj Palka, Juraj Mazur, Ivan Majercák, Andrej Dzupina, František Fazekas, Jozef Gonsorcik, Viliam Bugan, Juraj Selecky, Gabriel Kamensky, Jaroslava Strbova, Rudolf Smik, Andrej Dukat, Ivan Žuran, Janez Poklukar, Nataša Černič Šuligoj, Matija Cevc, Henry P Cyster, Naresh Ranjith, Clive Corbett, Junaid Bayat, Ellen Makoali Makotoko, Hendrik du Toit Theron, Ilse E Kapp, Matthys M de V Basson, Hanlie Lottering, Dina Van Aswegen, Louis J Van Zyl, Peter J Sebastian, Thayabran Pillay, Jan A Saaiman, Patrick J Commerford, Soraya Cassimjee, Garda Riaz, Iftikhar O Ebrahim, Mahomed Sarvan, Joseph H Mynhardt, Helmuth Reuter, Rajendran Moodley, Manuel Vida, Angel R. Cequier Fillat, Vicente Bodí Peris, Francisco Fuentes Jimenez, Francisco Marín, Jose M Cruz Fernández, Rafael Jesus Hidalgo Urbano, Blas Gil-Extremera, Pablo Toledo, Fernando Worner Diz, David Garcia-Dorado, Andres Iñiguez, José Tuñón Fernández, Jose R Gonzalez-Juanatey, Javier Fernandez Portales, Fernando Civeira Murillo, Laia Matas Pericas, Jose Luis Zamorano, Manuel De Mora Martin, Jordi Bruguera Cortada, Joaquin J Alonso Martin, Jose Maria Serrano Antolin, José R De Berrazueta Fernández, José Antonio Vázquez de Prada, Jose Francisco Díaz Fernández, José Alberto García Lledó, Juan Cosín Sales, Javier Botas Rodriguez, Gabriel Gusi Tragant, Amparo Benedicto, Carlos Gonzalez-Juanatey, Mercedes Camprubí Potau, Ignacio Plaza Perez, César Morís De La Tassa, Pablo Loma-Osorio Rincon, Javier Balaguer Recena, Juan M Escudier, Antonio Coca Payeras, Norberto Alonso Orcajo, Pedro Valdivielso, Godwin Constantine, Ruvaiz Haniffa, Nirmali Tissera, Stanley Amarasekera, Chandrike Ponnamperuma, Nimali Fernando, Kaputella Fernando, Jayanthimala Jayawardena, Santharaj Wijeyasingam, Gotabhaya Ranasinghe, Ruvan Ekanayaka, Sepalika Mendis, Vajira Senaratne, Gnanamoorthy Mayurathan, Thilak Sirisena, Ajantha Rajapaksha, Jagath I Herath, Naomali Amarasena, Stefan Berglund, Gundars Rasmanis, Ola Vedin, Nils Witt, Georgios Mourtzinis, Peter Nicol, Ole Hansen, Stefano Romeo, Steen Agergaard Jensen, Ingemar Torstensson, Ulf Ahremark, Torbjörn Sundelin, Tiziano Moccetti, Christian Müller, Francois Mach, Ronald Binde, Wei-Chuan Tsai, Kwo-Chang Ueng, Wen-Ter Lai, Ming-En Liu, Juey-Jen Hwang, Wei-Hsian Yin, I-Chang Hsieh, Ming-Jer Hsieh, Wei Hsiang Lin, Jen-Yuan Kuo, Tsuei-Yuan Huang, Chih-Yuan Fang, Pinij Kaewsuwanna, Wasant Soonfuang, Woravut Jintapakorn, Apichard Sukonthasarn, Nattawut Wongpraparut, Krisada Sastravaha, Nakarin Sansanayudh, Wirash Kehasukcharoen, Dilok Piyayotai, Paiboon Chotnoparatpat, Ahmet Camsari, Hakan Kultursay, Bulent Mutlu, Murat Ersanli, Mustafa Demirtas, Cevat Kirma, Ertan Ural, Lale Koldas, Oleksandr Karpenko, Alexander Prokhorov, Ihor Vakaluyk, Halyna Myshanych, Dmytro Reshotko, Valeriy Batushkin, Leonid Rudenko, Ihor Kovalskyi, Mykola Kushnir, Vira Tseluyko, Yuriy Mostovoy, Mykola Stanislavchuk, Yulian Kyiak, Yuriy Karpenko, Yaroslav Malynovsky, Andriy Klantsa, Oles Kutniy, Ekaterina Amosova, Viktor Tashchuk, Oleh Leshchuk, Mykola Rishko, Mykola Kopytsya, Andriy Yagensky, Mykola Vatutin, Andriy Bagriy, Olga M Barna, Olexiy Ushakov, Georgiy Dzyak, Borys Goloborodko, Anatolii Rudenko, Volodymyr Zheleznyy, Jasper Trevelyan, Azfar Zaman, Kaeng Lee, Andrew Moriarty, Rajesh K Aggarwal, Piers Clifford, Yuk-Ki Wong, Syed MR Iqbal, Eduardas Subkovas, Denise Braganza, David Sarkar, Robert Storey, Huw Griffiths, Sam McClure, Rangasamy Muthusamy, Simon Smith, John Kurian, Terry Levy, Craig Barr, Honer Kadr, Robert Gerber, Audrius Simaitis, Handrean Soran, Anthony Mathur, Adrian Brodison, Mohammad Ayaz, Muhammad Cheema, Richard Oliver, Simon Thackray, Telal Mudawi, Gohar Rahman, Ayyaz Sultan, David Sharman, David Sprigings, Rob Butler, Peter Wilkinson, Gregory YH Lip, Julian Halcox, Sean Gallagher, Nicholas Ossei-Gerning, Gil Vardi, Duccio Baldari, David Brabham, Charles Treasure II, Charles Dahl, Bruce Palmer, Alan Wiseman, Abul Khan, Sanjeev Puri, Ann Elizabeth Mohart, Carlos Ince, Enrique Flores, Scott Wright, Shi-Chi Cheng, Michael Rosenberg, William Rogers, Edward Kosinski, Les Forgosh, Jonathan Waltman, Misal Khan, Mohammad Shoukfeh, Georges Dagher, Patrick Cambier, Ira Lieber, Priya Kumar, Cara East, Perry Krichmar, Mian Hasan, Lindsey White, Thomas Knickelbine, Thomas Haldis, Eve Gillespie, Thomas Amidon, David Suh, Imran Arif, Mouhamad Abdallah, Faiq Akhter, Eric Carlson, Michael D'Urso, Fadi El-Ahdab, William Nelson, Katie Moriarty, Barry Harris, Steven Cohen, Luther Carter, Daniel Doty, Kenneth Sabatino, Tariq Haddad, Amir Malik, Sunder Rao, Angel Mulkay, Ion Jovin, Kim Klancke, Vinay Malhotra, Sai K Devarapalli, Michael Koren, Harish Chandna, George Dodds III, Tauqir Goraya, James Bengston, Matthew Janik, Joseph Moran, Andrew Sumner, John Kobayashi, William Davis, Shahram Yazdani, John Pasquini, Maitreya Thakkar, Amarnath Vedere, Wayne Leimbach, James Rider, Sarah Fenton, Narendra Singh, Anil V Shah, Denise Janosik, Carl Pepine, Brett Berman, Joseph Gelormini, Christopher Daniels, Kerensky Richard, Friederike Keating, Nicholas I Kondo, Sanjay Shetty, Howard Levite, Winfried Waider, Theodore Takata, Mazen Abu-Fadel, Vipul Shah, Rahul Aggarwal, Mark Izzo, Anil Kumar, Brack Hattler, Rose Do, Chad Link, Anna Bortnick, George Kinzfogl III, Arnold Ghitis, John Larry, Edward Teufel, Peter Kuhlman, Brent Mclaurin, Wenwu Zhang, Stephen Thew, Jalal Abbas, Matthew White, Othman Islam, Sumeet Subherwal, Nandkishore Ranadive, Babak Vakili, Christian Gring, David Henderson, Timothy Schuchard, Naim Farhat, Geoffrey Kline, Sharan Mahal, Jack Whitaker, Shawn Speirs, Rolf Andersen, Nizar Daboul, Phillip Horwitz, Firas Zahr, George Ponce, Zubair Jafar, Joseph Mcgarvey, Vipul Panchal, Stephen Voyce, Thomas Blok, William Sheldon, Masoud M Azizad, Carsten Schmalfuss, Mark Picone, Robert Pederson, William Herzog, Keith Friedman, Jason Lindsey, Rosemary Nowins, Eichenlaub Timothy, Parilak Leonard, Norman Lepor, Mahfouz El Shahawy, Howard Weintraub, Anand Irimpen, Alvaro Alonso, Wade May, Daniels Christopher, Thomas Galski, Alan Chu, Freny Mody, Ebrahimi Ramin, Zachary Hodes, Joseph Rossi, Gregory Rose, James Fairlamb, Charles Lambert, Ajit Raisinghani, Antonio Abbate, George Vetrovec, Marilyn King, Charles Carey, Jaime Gerber, Liwa Younis, Hyeun (Tom) Park, Mladen Vidovich, Thomas Knutson, Dennis Friedman, Fred Chaleff, Arthur Loussararian, Phillip Rozeman, Carey Kimmelstiel, Jeffrey Kuvin, Kevin Silver, Malcolm Foster, Glen Tonnessen, Andrey Espinoza, Mohamadali Amlani, Andreas Wali, Christopher Malozzi, Geert T Jong, Clara Massey, Keattiyoat Wattanakit, Philip J. O'Donnell, Dinesh Singal, Naseem Jaffrani, Sridhar Banuru, Daniel Fisher, Mark Xenakis, Neal Perlmutter, Ravi Bhagwat, James Strader, Ronald Blonder, Ayim Akyea-Djamson, Ajay Labroo, Kwan Lee, H. John Marais, Edmund Claxton, Robert Weiss, Rohr Kathryn, Martin Berk, Peter Rossi, Parag Joshi, Amit Khera, Ajit S Khaira, Greg Kumkumian, Steven Lupovitch, Joshua Purow, Stephen Welka, David Hoffman, Stuart Fischer, Eugene Soroka, Donald Eagerton, Samir Pancholy, Michael Ray, Norman Erenrich, Michael Farrar, Stewart Pollock, William J French, Steve Diamantis, Douglas Guy, Lawrence Gimple, Mark Neustel, Steven Schwartz, Edward Pereira, Seals Albert, Douglas Spriggs, Janet Strain, Suneet Mittal, Anthony Vo, Majed Chane, Jason Hall, Nampalli Vijay, Kapildeo Lotun, F. Martin Lester, Ahed Nahhas, Theodore Pope, Paul Nager, Rakesh Vohra, Mukesh Sharma, Riyaz Bashir, Hinan Ahmed, Michael Berlowitz, Robert Fishberg, Robert Barrucco, Eric Yang, Michael Radin, Daniel Sporn, Dwight Stapleton, Steven Eisenberg, Joel Landzberg, Martin Mcgough, Samir Turk, Michael Schwartz, P. Sandy Sundram, Diwakar Jain, Mark Zainea, Carlos Bayron, Ronald Karlsberg, Suhail Dohad, Henry Lui, William Keen, Donald Westerhausen, Sandeep Khurana, Himanshu Agarwal, Jessica Birchem, William Penny, Mark Chang, Sherrill Murphy, John Henry, Branislav Schifferdecker, John M Gilbert, Gopal Chalavarya, Charles Eaton, John F Schmedtje, Stuart Christenson, Imran Dotani, Douglas Denham, Alexander Macdonell, Paul Gibson, Aref Rahman, Tammam Al Joundi, Nizar Assi, Gary Conrad, Purushotham Kotha, Michael Love, Gregory Giesler, Howard Rubenstein, Dawood Gamil, Laura Akright, Justine Krawczyk, Joanne Cobler, Terry Wells, James Welker, Robert Foster, Richard Gilmore, Jay Anderson, Douglas Jacoby, Bill Harris, Geraldine Gardner, Ramprasad Dandillaya, Kishor Vora, John Kostis, John Hunter, David Laxson, Eric Ball, Renato Lopes, Flavia Egydio, Anelise Kawakami, Janaina Oliveira, Julianna Wozniak, Alexander Matthews, Caroline Ratky, Janine Valiris, Lisa Berdan, Anita Hepditch, Kirby Quintero, Tyrus Rorick, Melissa Westbrook, Andrea Pascual, Carla Rovito, Madeleine Bezault, Elodie Drouet, Tabassome Simon, Caroline Alsweiler, Anne Luyten, Julie Butters, Liddy Griffith, Michelle Shaw, Lena Grunberg, Shahidul Islam, Marie-France Brégeault, Nathalie Bougon, Douglas Faustino, Sylvie Fontecave, Judith Murphy, Melanie Verrier, Veronique Agnetti, Dorthe Andersen, Emmy Badreddine, Mhamed Bekkouche, Cecile Bouancheau, Imane Brigui, Maddy Brocklehurst, Joseph Cianciarulo, Dawn Devaul, Szilvia Domokos, Cecile Gache, Caroline Gobillot, Severine Guillou, Jan Healy, Megan Heath, Gayatri Jaiwal, Carine Javierre, Julien Labeirie, Myriam Monier, Ulises Morales, Asmaa Mrabti, Bicky Mthombeni, Betim Okan, Lucile Smith, Jennifer Sheller, Sebastien Sopena, Valerie Pellan, Fadela Benbernou, Nafissa Bengrait, Maud Lamoureux, Katarina Kralova, Michel Scemama, Raphael Bejuit, Anthony Coulange, Christelle Berthou, Jérôme Repincay, Christelle Lorenzato, Alexis Etienne, Valerie Gouet, Mickael Normand, Anne Ourliac, Christelle Rondel, Antony Adamo, Pascale Beltran, Pauline Barraud, Helene Dubois-Gache, Benjamin Halle, Lamia Metwally, Maxime Mourgues, Marc Sotty, Marion Vincendet, Raluca Cotruta, Zhu Chengyue, Dominique Fournie-Lloret, Christine Morrello, Aurelie Perthuis, Patrick Picault, Isabelle Zobouyan, Helen M. Colhoun, Michael A. Dempsey, Mark A McClanahan, Ray, K, Colhoun, H, Szarek, M, Baccara-Dinet, M, Bhatt, D, Bittner, V, Budaj, A, Diaz, R, Goodman, S, Hanotin, C, Harrington, R, Jukema, J, Loizeau, V, Lopes, R, Moryusef, A, Murin, J, Pordy, R, Ristic, A, Roe, M, Tunon, J, White, H, Zeiher, A, Schwartz, G, Steg, P, Tricoci, P, Mahaffey, K, Edelberg, J, Lecorps, G, Sasiela, W, Tamby, J, Aylward, P, Drexel, H, Sinnaeve, P, Dilic, M, Gotcheva, N, Prieto, J, Yong, H, Lopez-Jaramillo, P, Pecin, I, Reiner, Z, Ostadal, P, Viigimaa, M, Nieminen, M, Chumburidze, V, Marx, N, Danchin, N, Liberopoulos, E, Montenegro Valdovinos, P, Tse, H, Kiss, R, Xavier, D, Zahger, D, Valgimigli, M, Kimura, T, Kim, H, Kim, S, Erglis, A, Laucevicius, A, Kedev, S, Yusoff, K, Ramos Lopez, G, Alings, M, Halvorsen, S, Correa Flores, R, Morais, J, Dorobantu, M, Karpov, Y, Chua, T, Fras, Z, Dalby, A, de Silva, H, Hagstrom, E, Landmesser, U, Chiang, C, Sritara, P, Guneri, S, Parkhomenko, A, Moriarty, P, Vogel, R, Chaitman, B, Kelsey, S, Olsson, A, Rouleau, J, Simoons, M, Alexander, K, Meloni, C, Rosenson, R, Sijbrands, E, Alexander, J, Armaganijan, L, Bagai, A, Bahit, M, Brennan, J, Clifton, S, Devore, A, Deloatch, S, Dickey, S, Dombrowski, K, Ducrocq, G, Eapen, Z, Endsley, P, Eppinger, A, Harrison, R, Hess, C, Hlatky, M, Jordan, J, Knowles, J, Kolls, B, Kong, D, Leonardi, S, Lillis, L, Maron, D, Marcus, J, Mathews, R, Mehta, R, Mentz, R, Moreira, H, Patel, C, Bernardez-Pereira, S, Perkins, L, Povsic, T, Puymirat, E, Schuyler Jones, W, Shah, B, Sherwood, M, Stringfellow, K, Sujjavanich, D, Toma, M, Trotter, C, Van Diepen, S, Wilson, M, Yan, A, Schiavi, L, Garrido, M, Alvarisqueta, A, Sassone, S, Bordonava, A, Alves De Lima, A, Schmidberg, J, Duronto, E, Caruso, O, Novaretto, L, Hominal, M, Montana, O, Caccavo, A, Gomez Vilamajo, O, Lorenzatti, A, Cartasegna, L, Paterlini, G, Mackinnon, I, Caime, G, Amuchastegui, M, Salomone, O, Codutti, O, Jure, H, Bono, J, Hrabar, A, Vallejos, J, Ahuad Guerrero, R, Novoa, F, Patocchi, C, Zaidman, C, Giuliano, M, Dran, R, Vico, M, Carnero, G, Guzman, P, Medrano Allende, J, Garcia Brasca, D, Bustamante Labarta, M, Nani, S, Blumberg, E, Colombo, H, Liberman, A, Fuentealba, V, Luciardi, H, Waisman, G, Berli, M, Garcia Duran, R, Cestari, H, Luquez, H, Giordano, J, Saavedra, S, Zapata, G, Costamagna, O, Llois, S, Waites, J, Collins, N, Soward, A, Hii, C, Shaw, J, Arstall, M, Horowitz, J, Ninio, D, Rogers, J, Colquhoun, D, Oqueli Flores, R, Roberts-Thomson, P, Raffel, O, Lehman, S, Aroney, C, Coverdale, S, Garrahy, P, Starmer, G, Sader, M, Carroll, P, Dick, R, Zweiker, R, Hoppe, U, Huber, K, Berger, R, Delle-Karth, G, Frey, B, Weidinger, F, Faes, D, Hermans, K, Pirenne, B, Leone, A, Hoffer, E, Vrolix, M, De Wolf, L, Wollaert, B, Castadot, M, Dujardin, K, Beauloye, C, Vervoort, G, Striekwold, H, Convens, C, Roosen, J, Barbato, E, Claeys, M, Cools, F, Terzic, I, Barakovic, F, Midzic, Z, Pojskic, B, Fazlibegovic, E, Kulic, M, Durak-Nalbantic, A, Vulic, D, Muslibegovic, A, Goronja, B, Reis, G, Sousa, L, Nicolau, J, Giorgeto, F, Silva, R, Nigro Maia, L, Rech, R, Rossi, P, Cerqueira, M, Duda, N, Kalil, R, Kormann, A, Abrantes, J, Pimentel Filho, P, Soggia, A, de Santos, M, Neuenschwander, F, Bodanese, L, Michalaros, Y, Eliaschewitz, F, Vidotti, M, Leaes, P, Botelho, R, Kaiser, S, Manenti, E, Precoma, D, Moura Jorge, J, de B Silva, P, Silveira, J, Saporito, W, Marin-Neto, J, Feitosa, G, Ritt, L, de Souza, J, Costa, F, Souza, W, Reis, H, Machado, L, Ayoub, J, Todorov, G, Nikolov, F, Velcheva, E, Tzekova, M, Benov, H, Petranov, S, Tumbev, H, Shehova-Yankova, N, Markov, D, Raev, D, Mollov, M, Kichukov, K, Ilieva-Pandeva, K, Ivanova, R, Gospodinov, M, Mincheva, V, Lazov, P, Dimov, B, Senaratne, M, Stone, J, Kornder, J, Pearce, S, Dion, D, Savard, D, Pesant, Y, Pandey, A, Robinson, S, Gosselin, G, Vizel, S, Hoag, G, Bourgeois, R, Morisset, A, Sabbah, E, Sussex, B, Kouz, S, Macdonald, P, Diaz, A, Michaud, N, Fell, D, Leung, R, Vuurmans, T, Lai, C, Nigro, F, Davies, R, Nogareda, G, Vijayaraghavan, R, Ducas, J, Lepage, S, Mehta, S, Cha, J, Dupuis, R, Fong, P, Lutchmedial, S, Rodes-Cabau, J, Fadlallah, H, Cleveland, D, Huynh, T, Bata, I, Hameed, A, Pincetti, C, Potthoff, S, Acevedo, M, Aguirre, A, Vejar, M, Yanez, M, Araneda, G, Fernandez, M, Perez, L, Varleta, P, Florenzano, F, Huidobro, L, Raffo, C, Olivares, C, Nahuelpan, L, Montecinos, H, Chen, J, Dong, Y, Huang, W, Wang, J, Huang, S, Yao, Z, Li, X, Cui, L, Lin, W, Sun, Y, Li, J, Zhang, X, Zhu, H, Chen, D, Huang, L, Dong, S, Su, G, Xu, B, Su, X, Cheng, X, Lin, J, Zong, W, Li, H, Feng, Y, Xu, D, Yang, X, Ke, Y, Lin, X, Zhang, Z, Zheng, Z, Luo, Z, Chen, Y, Ding, C, Zhong, Y, Zheng, Y, Peng, D, Zhao, S, Li, Y, Liu, X, Wei, M, Liu, S, Yu, Y, Qu, B, Jiang, W, Zhou, Y, Zhao, X, Yuan, Z, Guo, Y, Xu, X, Shi, X, Ge, J, Fu, G, Bai, F, Fang, W, Shou, X, Xiang, M, Lu, Q, Zhang, R, Zhu, J, Xu, Y, Fan, Z, Li, T, Wu, C, Jaramillo, N, Sanchez Vallejo, G, Luna Botia, D, Botero Lopez, R, Molina De Salazar, D, Cadena Bonfanti, A, Cotes Aroca, C, Diego Higuera, J, Blanquicett, M, Barrera Silva, S, Garcia Lozada, H, Coronel Arroyo, J, Accini Mendoza, J, Fernandez Ruiz, R, Quintero Ossa, A, Manzur Jatin, F, Sotomayor Herazo, A, Castellanos Parada, J, Suarez Arambula, R, Urina Triana, M, Fernandez Trujillo, A, Strozzi, M, Car, S, Jeric, M, Milicic, D, Bencic, M, Pintaric, H, Prvulovic, D, Sikic, J, Persic, V, Mileta, D, Stambuk, K, Babic, Z, Tomulic, V, Lukenda, J, Mejic-Krstulovic, S, Starcevic, B, Spinar, J, Horak, D, Velicka, Z, Stasek, J, Alan, D, Machova, V, Linhart, A, Novotny, V, Kaucak, V, Rokyta, R, Naplava, R, Coufal, Z, Adamkova, V, Podpera, I, Zizka, J, Motovska, Z, Marusincova, I, Svab, P, Heinc, P, Kuchar, J, Povolny, P, Matuska, J, Poulsen, S, Raungaard, B, Clemmensen, P, Bang, L, May, O, Bottcher, M, Hove, J, Frost, L, Gislason, G, Larsen, J, Betton Johansen, P, Hald, F, Johansen, P, Jeppesen, J, Nielsen, T, Kristensen, K, Walichiewicz, P, Lomholdt, J, Klausen, I, Nielsen, P, Davidsen, F, Videbaek, L, Soots, M, Vahula, V, Hedman, A, Soopold, U, Martsin, K, Jurgenson, T, Kristjan, A, Helsinki, J, Vikman, S, Huikuri, H, Airaksinen, J, Coste, P, Ferrari, E, Morel, O, Montalescot, G, Machecourt, J, Barone-Rochette, G, Mansourati, J, Cottin, Y, Leclercq, F, Belhassane, A, Delarche, N, Boccara, F, Paganelli, F, Clerc, J, Schiele, F, Aboyans, V, Probst, V, Berland, J, Lefevre, T, Citron, B, Khintibidze, I, Shaburishvili, T, Pagava, Z, Ghlonti, R, Lominadze, Z, Khabeishvili, G, Hemetsberger, R, Edward, K, Rauch-Krohnert, U, Stratmann, M, Appel, K, Schmidt, E, Omran, H, Stellbrink, C, Dorsel, T, Lianopoulos, E, Vohringer, H, Marx, R, Zirlik, A, Schellenberg, D, Heitzer, T, Laufs, U, Werner, C, Gielen, S, Nuding, S, Winkelmann, B, Behrens, S, Sydow, K, Karakas, M, Simonis, G, Muenzel, T, Werner, N, Leggewie, S, Bocker, D, Braun-Dullaeus, R, Toursarkissian, N, Jeserich, M, Weissbrodt, M, Schaeufele, T, Weil, J, Voller, H, Waltenberger, J, Natour, M, Schmitt, S, Muller-Wieland, D, Steiner, S, Heidenreich, L, Offers, E, Gremmler, U, Killat, H, Rieker, W, Patsilinakos, S, Kartalis, A, Manolis, A, Sionis, D, Chachalis, G, Skoumas, I, Athyros, V, Vardas, P, Parthenakis, F, Alexopoulos, D, Hahalis, G, Lekakis, J, Hatzitolios, A, Fausto Ovando, S, Arango Benecke, J, Rodriguez De Leon, E, Yan, B, Siu, D, Turi, T, Merkely, B, Ungi, I, Lupkovics, G, Nagy, L, Katona, A, Edes, I, Muller, G, Horvath, I, Kapin, T, Szigeti, Z, Falukozy, J, Kumbla, M, Sandhu, M, Annam, S, Proddutur, N, Regella, R, Premchand, R, Mahajan, A, Pawar, S, Abhyanakar, A, Kerkar, P, Govinda, R, Oomman, A, Sinha, D, Patil, S, Kahali, D, Sawhney, J, Joshi, A, Chaudhary, S, Harkut, P, Guha, S, Porwal, S, Jujjuru, S, Pothineni, R, Monteiro, M, Khan, A, Iyengar, S, Grewal, J, Chopda, M, Fulwani, M, Patange, A, Sachin, P, Chopra, V, Goyal, N, Shinde, R, Manakshe, G, Patki, N, Sethi, S, Munusamy, V, Karna, S, Thanvi, S, Adhyapak, S, Patil, C, Pandurangi, U, Mathur, R, Gupta, J, Kalashetti, S, Bhagwat, A, Raghuraman, B, Yerra, S, Bhansali, P, Borse, R, Rahul, P, Das, S, Kumar, V, Abdullakutty, J, Saathe, S, Palimkar, P, Sathe, S, Atar, S, Shechter, M, Mosseri, M, Arbel, Y, Ehud, C, Ofer, H, Lotan, C, Rosenschein, U, Katz, A, Henkin, Y, Francis, A, Klutstein, M, Nikolsky, E, Zukermann, R, Turgeman, Y, Halabi, M, Marmor, A, Kornowski, R, Jonas, M, Amir, O, Hasin, Y, Rozenman, Y, Fuchs, S, Zvi, V, Hussein, O, Gavish, D, Vered, Z, Caraco, Y, Elias, M, Tov, N, Wolfovitz, E, Lishner, M, Elias, N, Piovaccari, G, De Pellegrin, A, Garbelotto, R, Guardigli, G, Marco, V, Licciardello, G, Auguadro, C, Scalise, F, Cuccia, C, Salvioni, A, Musumeci, G, Senni, M, Calabro, P, Novo, S, Faggiano, P, Metra, M, De Cesare, N, Berti, S, Cavallini, C, Puccioni, E, Galvani, M, Tespili, M, Piatti, P, Palvarini, M, De Luca, G, Violini, R, De Leo, A, Olivari, Z, Perrone Filardi, P, Ferratini, M, Racca, V, Dai, K, Shimatani, Y, Kamiya, H, Ando, K, Takeda, Y, Morino, Y, Hata, Y, Kimura, K, Kishi, K, Michishita, I, Uehara, H, Higashikata, T, Hirayama, A, Hirooka, K, Doi, Y, Sakagami, S, Taguchi, S, Koike, A, Fujinaga, H, Koba, S, Kozuma, K, Kawasaki, T, Ono, Y, Shimizu, M, Katsuda, Y, Wada, A, Shinke, T, Ako, J, Fujii, K, Takahashi, T, Sakamoto, T, Nakao, K, Furukawa, Y, Sugino, H, Tamura, R, Mano, T, Uematsu, M, Utsu, N, Ito, K, Haraguchi, T, Sato, K, Ueda, Y, Nishibe, A, Fujimoto, K, Masutani, M, Yoon, J, Park, H, Chae, I, Kim, M, Jeong, M, Rha, S, Kim, C, Hong, T, Tahk, S, Kim, Y, Busmane, A, Pontaga, N, Strelnieks, A, Mintale, I, Sime, I, Petrulioniene, Z, Kavaliauskiene, R, Jurgaitiene, R, Sakalyte, G, Slapikas, R, Norkiene, S, Misonis, N, Kibarskis, A, Kubilius, R, Bojovski, S, Lozance, N, Kjovkaroski, A, Doncovska, S, Ong, T, Kasim, S, Maskon, O, Kandasamy, B, Liew, H, Wan Mohamed, W, Garcia Castillo, A, Carrillo Calvillo, J, Fajardo Campos, P, Nunez Fragoso, J, Bayram Llamas, E, Alcocer Gamba, M, Carranza Madrigal, J, Gonzalez Salas, L, Lopez Rosas, E, Gonzalez Diaz, B, Salcido Vazquez, E, Nacoud Ackar, A, Llamas Esperon, G, Martinez Sanchez, C, Guerrero De Leon, M, Suarez Otero, R, Fanghanel Salmon, G, Perez Rios, J, Garza Ruiz, J, Breedveld, R, Feenema-Aardema, M, Borger-Van Der Burg, A, Hoogslag, P, Suryapranata, H, Oomen, A, Van Haelst, P, Wiersma, J, Basart, D, Van Der Wal, R, Zwart, P, Monraats, P, Van Kesteren, H, Karalis, I, Verdel, G, Brueren, B, Troquay, R, Viergever, E, Al-Windy, N, Bartels, G, Cornel, J, Hermans, W, Herrman, J, Bos, R, Groutars, R, Van Der Zwaan, C, Kaplan, R, Lionarons, R, Ronner, E, Groenemeijer, B, Bronzwaer, P, Liem, A, Rensing, B, Bokern, M, Nijmeijer, R, Hersbach, F, Willems, F, Gosselink, A, Rasoul, S, Elliott, J, Wilkins, G, Fisher, R, Scott, D, Hart, H, Stewart, R, Harding, S, Ternouth, I, Fisher, N, Wilson, S, Aitken, D, Anscombe, R, Davidson, L, Tomala, T, Nygard, O, Sparby, J, Andersen, K, Gullestad, L, Jortveit, J, Munk, P, Singsaas, E, Hurtig, U, Calderon Ticona, J, Durand Velasquez, J, Negron Miguel, S, Sanabria Perez, E, Carrion Chambilla, J, Chavez Ayala, C, Castillo Leon, R, Vargas Gonzales, R, Hernandez Zuniga, J, Camacho Cosavalente, L, Bravo Mannucci, J, Heredia Landeo, J, Llerena Navarro, N, Roldan Concha, Y, Rodriguez Chavez, V, Anchante Hernandez, H, Zea Nunez, C, Mogrovejo Ramos, W, Ferrolino, A, Sy, R, Tirador, L, Matiga, G, Coching, R, Bernan, A, Rogelio, G, Morales, D, Tan, E, Sulit, D, Wlodarczak, A, Jaworska, K, Skonieczny, G, Pawlowicz, L, Wojewoda, P, Busz-Papiez, B, Bednarski, J, Goch, A, Staneta, P, Dulak, E, Saminski, K, Krasowski, W, Sudnik, W, Zurakowski, A, Skorski, M, Miklaszewicz, B, Kubica, J, Andrzej Lipko, J, Kostarska-Srokosz, E, Piepiorka, M, Drzewiecka, A, Stasiewski, A, Blicharski, T, Bystryk, L, Szpajer, M, Korol, M, Czerski, T, Mirek-Bryniarska, E, Gniot, J, Lubinski, A, Gorny, J, Franek, E, Raczak, G, Szwed, H, Monteiro, P, Mesquita Bastos, J, Pereira, H, Martins, D, Seixo, F, Mendonca, C, Botelho, A, Caetano, F, Minescu, B, Istratoaie, O, Tesloianu, D, Cristian, G, Dumitrescu, S, Podoleanu, C, Constantinescu, M, Bengus, C, Militaru, C, Rosu, D, Parepa, I, Matei, A, Alexandru, T, Malis, M, Coman, I, Stanescu-Cioranu, R, Dimulescu, D, Shvarts, Y, Orlikova, O, Kobalava, Z, Barbarash, O, Markov, V, Lyamina, N, Gordienko, A, Zrazhevsky, K, Vishnevsky, A, Gurevich, V, Stryuk, R, Lomakin, N, Bokarev, I, Khlevchuk, T, Shalaev, S, Khaisheva, L, Chizhov, P, Viktorova, I, Osokina, N, Shchekotov, V, Akatova, E, Chumakova, G, Libov, I, Voevoda, M, Tretyakova, T, Baranov, E, Shustov, S, Yakushin, S, Gordeev, I, Khasanov, N, Reshetko, O, Sotnikova, T, Molchanova, O, Nikolaev, K, Gapon, L, Baranova, E, Shogenov, Z, Kosmachova, E, Povzun, A, Egorova, L, Tyrenko, V, Ivanov, I, Ilya, M, Kanorsky, S, Simic, D, Ivanovic, N, Davidovic, G, Tasic, N, Asanin, M, Stojic, S, Apostolovic, S, Ilic, S, Putnikovic Tosic, B, Stankovic, A, Arandjelovic, A, Radovanovic, S, Todic, B, Balinovac, J, Dincic, D, Seferovic, P, Karadzic, A, Dodic, S, Dimkovic, S, Jakimov, T, Poh, K, Ong, H, Tang I-Shing, J, Micko, K, Nociar, J, Pella, D, Fulop, P, Hranai, M, Palka, J, Mazur, J, Majercak, I, Dzupina, A, Fazekas, F, Gonsorcik, J, Bugan, V, Selecky, J, Kamensky, G, Strbova, J, Smik, R, Dukat, A, Zuran, I, Poklukar, J, Cernic Suligoj, N, Cevc, M, Cyster, H, Ranjith, N, Corbett, C, Bayat, J, Makotoko, E, du Toit Theron, H, Kapp, I, de V Basson, M, Lottering, H, Van Aswegen, D, Van Zyl, L, Sebastian, P, Pillay, T, Saaiman, J, Commerford, P, Cassimjee, S, Riaz, G, Ebrahim, I, Sarvan, M, Mynhardt, J, Reuter, H, Moodley, R, Vida, M, Cequier Fillat, A, Bodi Peris, V, Fuentes Jimenez, F, Marin, F, Cruz Fernandez, J, Hidalgo Urbano, R, Gil-Extremera, B, Toledo, P, Worner Diz, F, Garcia-Dorado, D, Iniguez, A, Gonzalez-Juanatey, J, Fernandez Portales, J, Civeira Murillo, F, Matas Pericas, L, Zamorano, J, De Mora Martin, M, Bruguera Cortada, J, Alonso Martin, J, Serrano Antolin, J, De Berrazueta Fernandez, J, Vazquez de Prada, J, Diaz Fernandez, J, Garcia Lledo, J, Cosin Sales, J, Botas Rodriguez, J, Gusi Tragant, G, Benedicto, A, Gonzalez-Juanatey, C, Camprubi Potau, M, Plaza Perez, I, De La Tassa, C, Loma-Osorio Rincon, P, Balaguer Recena, J, Escudier, J, Payeras, A, Alonso Orcajo, N, Valdivielso, P, Constantine, G, Haniffa, R, Tissera, N, Amarasekera, S, Ponnamperuma, C, Fernando, N, Fernando, K, Jayawardena, J, Wijeyasingam, S, Ranasinghe, G, Ekanayaka, R, Mendis, S, Senaratne, V, Mayurathan, G, Sirisena, T, Rajapaksha, A, Herath, J, Amarasena, N, Berglund, S, Rasmanis, G, Vedin, O, Witt, N, Mourtzinis, G, Nicol, P, Hansen, O, Romeo, S, Agergaard Jensen, S, Torstensson, I, Ahremark, U, Sundelin, T, Moccetti, T, Muller, C, Mach, F, Binde, R, Tsai, W, Ueng, K, Lai, W, Liu, M, Hwang, J, Yin, W, Hsieh, I, Hsieh, M, Kuo, J, Huang, T, Fang, C, Kaewsuwanna, P, Soonfuang, W, Jintapakorn, W, Sukonthasarn, A, Wongpraparut, N, Sastravaha, K, Sansanayudh, N, Kehasukcharoen, W, Piyayotai, D, Chotnoparatpat, P, Camsari, A, Kultursay, H, Mutlu, B, Ersanli, M, Demirtas, M, Kirma, C, Ural, E, Koldas, L, Karpenko, O, Prokhorov, A, Vakaluyk, I, Myshanych, H, Reshotko, D, Batushkin, V, Rudenko, L, Kovalskyi, I, Kushnir, M, Tseluyko, V, Mostovoy, Y, Stanislavchuk, M, Kyiak, Y, Karpenko, Y, Malynovsky, Y, Klantsa, A, Kutniy, O, Amosova, E, Tashchuk, V, Leshchuk, O, Rishko, M, Kopytsya, M, Yagensky, A, Vatutin, M, Bagriy, A, Barna, O, Ushakov, O, Dzyak, G, Goloborodko, B, Rudenko, A, Zheleznyy, V, Trevelyan, J, Zaman, A, Lee, K, Moriarty, A, Aggarwal, R, Clifford, P, Wong, Y, Iqbal, S, Subkovas, E, Braganza, D, Sarkar, D, Storey, R, Griffiths, H, Mcclure, S, Muthusamy, R, Smith, S, Kurian, J, Levy, T, Barr, C, Kadr, H, Gerber, R, Simaitis, A, Soran, H, Mathur, A, Brodison, A, Ayaz, M, Cheema, M, Oliver, R, Thackray, S, Mudawi, T, Rahman, G, Sultan, A, Sharman, D, Sprigings, D, Butler, R, Wilkinson, P, Lip, G, Halcox, J, Gallagher, S, Ossei-Gerning, N, Vardi, G, Baldari, D, Brabham, D, Treasure II, C, Dahl, C, Palmer, B, Wiseman, A, Puri, S, Mohart, A, Ince, C, Flores, E, Wright, S, Cheng, S, Rosenberg, M, Rogers, W, Kosinski, E, Forgosh, L, Waltman, J, Khan, M, Shoukfeh, M, Dagher, G, Cambier, P, Lieber, I, Kumar, P, East, C, Krichmar, P, Hasan, M, White, L, Knickelbine, T, Haldis, T, Gillespie, E, Amidon, T, Suh, D, Arif, I, Abdallah, M, Akhter, F, Carlson, E, D'Urso, M, El-Ahdab, F, Nelson, W, Moriarty, K, Harris, B, Cohen, S, Carter, L, Doty, D, Sabatino, K, Haddad, T, Malik, A, Rao, S, Mulkay, A, Jovin, I, Klancke, K, Malhotra, V, Devarapalli, S, Koren, M, Chandna, H, Dodds III, G, Goraya, T, Bengston, J, Janik, M, Moran, J, Sumner, A, Kobayashi, J, Davis, W, Yazdani, S, Pasquini, J, Thakkar, M, Vedere, A, Leimbach, W, Rider, J, Fenton, S, Singh, N, Shah, A, Janosik, D, Pepine, C, Berman, B, Gelormini, J, Daniels, C, Richard, K, Keating, F, Kondo, N, Shetty, S, Levite, H, Waider, W, Takata, T, Abu-Fadel, M, Shah, V, Izzo, M, Kumar, A, Hattler, B, Do, R, Link, C, Bortnick, A, Kinzfogl III, G, Ghitis, A, Larry, J, Teufel, E, Kuhlman, P, Mclaurin, B, Zhang, W, Thew, S, Abbas, J, White, M, Islam, O, Subherwal, S, Ranadive, N, Vakili, B, Gring, C, Henderson, D, Schuchard, T, Farhat, N, Kline, G, Mahal, S, Whitaker, J, Speirs, S, Andersen, R, Daboul, N, Horwitz, P, Zahr, F, Ponce, G, Jafar, Z, Mcgarvey, J, Panchal, V, Voyce, S, Blok, T, Sheldon, W, Azizad, M, Schmalfuss, C, Picone, M, Pederson, R, Herzog, W, Friedman, K, Lindsey, J, Nowins, R, Timothy, E, Leonard, P, Lepor, N, El Shahawy, M, Weintraub, H, Irimpen, A, Alonso, A, May, W, Christopher, D, Galski, T, Chu, A, Mody, F, Ramin, E, Hodes, Z, Rossi, J, Rose, G, Fairlamb, J, Lambert, C, Raisinghani, A, Abbate, A, Vetrovec, G, King, M, Carey, C, Gerber, J, Younis, L, Vidovich, M, Knutson, T, Friedman, D, Chaleff, F, Loussararian, A, Rozeman, P, Kimmelstiel, C, Kuvin, J, Silver, K, Foster, M, Tonnessen, G, Espinoza, A, Amlani, M, Wali, A, Malozzi, C, Jong, G, Massey, C, Wattanakit, K, O'Donnell, P, Singal, D, Jaffrani, N, Banuru, S, Fisher, D, Xenakis, M, Perlmutter, N, Bhagwat, R, Strader, J, Blonder, R, Akyea-Djamson, A, Labroo, A, Marais, H, Claxton, E, Weiss, R, Kathryn, R, Berk, M, Joshi, P, Khera, A, Khaira, A, Kumkumian, G, Lupovitch, S, Purow, J, Welka, S, Hoffman, D, Fischer, S, Soroka, E, Eagerton, D, Pancholy, S, Ray, M, Erenrich, N, Farrar, M, Pollock, S, French, W, Diamantis, S, Guy, D, Gimple, L, Neustel, M, Schwartz, S, Pereira, E, Albert, S, Spriggs, D, Strain, J, Mittal, S, Vo, A, Chane, M, Hall, J, Vijay, N, Lotun, K, Lester, F, Nahhas, A, Pope, T, Nager, P, Vohra, R, Sharma, M, Bashir, R, Ahmed, H, Berlowitz, M, Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Stapleton, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, P, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Dohad, S, Lui, H, Keen, W, Westerhausen, D, Khurana, S, Agarwal, H, Birchem, J, Penny, W, Chang, M, Murphy, S, Henry, J, Schifferdecker, B, Gilbert, J, Chalavarya, G, Eaton, C, Schmedtje, J, Christenson, S, Dotani, I, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Assi, N, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Gamil, D, Akright, L, Krawczyk, J, Cobler, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, Egydio, F, Kawakami, A, Oliveira, J, Wozniak, J, Matthews, A, Ratky, C, Valiris, J, Berdan, L, Hepditch, A, Quintero, K, Rorick, T, Westbrook, M, Pascual, A, Rovito, C, Bezault, M, Drouet, E, Simon, T, Alsweiler, C, Luyten, A, Butters, J, Griffith, L, Shaw, M, Grunberg, L, Islam, S, Bregeault, M, Bougon, N, Faustino, D, Fontecave, S, Murphy, J, Verrier, M, Agnetti, V, Andersen, D, Badreddine, E, Bekkouche, M, Bouancheau, C, Brigui, I, Brocklehurst, M, Cianciarulo, J, Devaul, D, Domokos, S, Gache, C, Gobillot, C, Guillou, S, Healy, J, Heath, M, Jaiwal, G, Javierre, C, Labeirie, J, Monier, M, Morales, U, Mrabti, A, Mthombeni, B, Okan, B, Smith, L, Sheller, J, Sopena, S, Pellan, V, Benbernou, F, Bengrait, N, Lamoureux, M, Kralova, K, Scemama, M, Bejuit, R, Coulange, A, Berthou, C, Repincay, J, Lorenzato, C, Etienne, A, Gouet, V, Normand, M, Ourliac, A, Rondel, C, Adamo, A, Beltran, P, Barraud, P, Dubois-Gache, H, Halle, B, Metwally, L, Mourgues, M, Sotty, M, Vincendet, M, Cotruta, R, Chengyue, Z, Fournie-Lloret, D, Morrello, C, Perthuis, A, Picault, P, Zobouyan, I, Dempsey, M, Mcclanahan, M, ODYSSEY OUTCOMES Comm Investigato, and Ege Üniversitesi

Subjects
Male, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, STATIN THERAPY, blood-glucose, Endocrinology, Diabetes and Metabolism, GUIDELINES, PCSK9, 0302 clinical medicine, Endocrinology, GENETIC-VARIANTS, Cardiovascular Disease, Diabetes Complication, Aged Antibodies, Monoclonal, Humanized / therapeutic use* Cardiovascular Diseases / blood Cardiovascular Diseases / prevention & control* Diabetes Complications / blood Diabetes Complications / prevention & control* Female Humans Male Middle Aged Substances, Clinical endpoint, Medicine, guidelines, 030212 general & internal medicine, Prediabetes, Myocardial infarction, myocardial-infarction, genetic-variants, statin therapy, risk, pcsk9, association, liraglutide, evolocumab, RISK, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, BLOOD-GLUCOSE, ASSOCIATION, Middle Aged, Cardiovascular Diseases, Female, Life Sciences & Biomedicine, Human, medicine.medical_specialty, Acute coronary syndrome, PCSK9 inhibitor, acute coronary syndrome, lipoprotein(a), low-density lipoprotein cholesterol, 030209 endocrinology & metabolism, Antibodies, Monoclonal, Humanized, Diabetes Complications, Endocrinology & Metabolism, 03 medical and health sciences, Diabetes mellitus, Internal medicine, Internal Medicine, Humans, Aged, Alirocumab, diabetes, PCSK9, hyperlipidemia, Science & Technology, ODYSSEY OUTCOMES Committees and Investigators, business.industry, Unstable angina, EVOLOCUMAB, medicine.disease, MYOCARDIAL-INFARCTION, LIRAGLUTIDE, Human medicine, business
Abstract

Doi, Yasuji/0000-0002-8368-0827; galvani, marcello/0000-0001-5897-667X; Gislason, Gunnar H/0000-0002-0548-402X; Taskinen, Marja-Riitta/0000-0002-6229-3588; Sherwood, Matthew/0000-0002-4305-5883; Malynovsky, Yaroslav V/0000-0002-9118-1104; Viktorova, vic-inna@mail.ru I.A./0000-0001-8728-2722; bastos, jose/0000-0002-9526-3123; Yang, Eric H/0000-0003-4889-7454; Rudenko, Anatoliy Viktorovich/0000-0003-1099-1613; Novotny, Vojtech/0000-0003-3521-9945; Nikolaev, Konstantin/0000-0003-4601-6203; Reshetko, Olga/0000-0003-3107-7636; Leonardi, Sergio/0000-0002-4800-6132; Muenzel, Thomas/0000-0001-5503-4150; Ushakov, Alexei V/0000-0002-7020-4442; Tse, Hung Fat/0000-0002-9578-7808; Podoleanu, Cristian/0000-0001-9987-2519; Raffel, Owen C/0000-0001-5470-7050; Khasanov, Niiaz/0000-0002-7760-0763; Chumakova, Galina A/0000-0002-2810-6531; Ersanli, Murat/0000-0003-1847-3087; cornel, jan hein/0000-0002-1006-2112; Abbate, Antonio/0000-0002-1930-785X; Racca, Vittorio/0000-0002-4465-3789; Urina-Triana, Miguel A/0000-0001-6003-4622; Rasputina, Lesia/0000-0003-1230-4039; Racca, Vittorio/0000-0002-4465-3789; Reis, Gilmar/0000-0002-4847-1034; Sandhu, Manjinder/0000-0003-2538-2079; Keskin, Kudret/0000-0002-9049-1530; PAREPA, IRINEL/0000-0002-7571-9015; Manakshe, Gajendra/0000-0002-4983-4271; Nicolau, Jose C/0000-0002-9680-3689; Strelnieks, Aldis/0000-0003-3493-2562; Budaj, Andrzej/0000-0002-6395-2098; Marin, Francisco/0000-0001-7246-7708; Wongpraparut, Nattawut/0000-0002-1541-3313; Yuan, Zuyi/0000-0002-4141-0298; Jeong, Myung Ho/0000-0003-2424-810X; Mostovoy, Yuriy/0000-0002-7041-1230; Pepine, Carl/0000-0002-6011-681X; Lopez-Jaramillo, Patricio/0000-0002-9122-8742; Garcia-Lledo, Alberto/0000-0002-8986-2584; Tesloianu, Nicolae-Dan/0000-0002-1007-3022; Kosmacheva, Elena/0000-0001-8600-0199; Kunz Sebba Barroso Souza, Weimar/0000-0002-1265-1930; Katz, Amos/0000-0003-0422-934X; Tunon, Jose/0000-0002-1373-0999; Acevedo, Monica/0000-0002-7989-6633; Hove, Jens/0000-0002-5600-5623; Yakushin, Sergey/0000-0001-7202-742X; Gonzalez Juanatey, Jose Ramon/0000-0001-9681-3388; Lyamina, Nadezhda/0000-0001-6939-3234; Aylward, Philip/0000-0002-5358-8552; Apostolovic, Svetlana/0000-0001-9015-297X; Airaksinen, Juhani/0000-0002-0193-568X; Nahhas, Prof. Dr. Ahmed/0000-0002-2887-8187; Barbarash, Olga/0000-0002-4642-3610, WOS: 000475553300016, PubMed: 31272931, Background After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1.4-1.8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. Methods ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1-12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1: 1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0.65-1.30 mmol/L. in this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)-defined on the basis of patient history, review of medical records, or baseline HbA(1c) or fasting serum glucose-and risk of new-onset diabetes among those without diabetes at baseline. the primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials. gov, number NCT01663402. Findings At study baseline, 5444 patients (28.8%) had diabetes, 8246 (43.6%) had prediabetes, and 5234 (27.7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2.20-2.28 mmol/L), after 4 months' treatment with alirocumab (0.80 mmol/L), or after 4 months' treatment with placebo (2.25-2.28 mmol/L). in the placebo group, the incidence of the primary endpoint over a median of 2.8 years was greater in patients with diabetes (16.4%) than in those with prediabetes (9.2%) or normoglycaemia (8.5%); hazard ratio (HR) for diabetes versus normoglycaemia 2.09 (95% CI 1.78-2.46, p, Sanofi; Regeneron Pharmaceuticals, Sanofi and Regeneron Pharmaceuticals.

Published
2019

25. Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patients: The ODYSSEY OPTIONS II randomized trial

Author

Corinne Hanotin, Peter B. Jones, Elisabeth Steinhagen-Thiessen, Maurizio Averna, Helen M. Colhoun, Yunling Du, Stephen Donahue, Randall Severance, Michel Farnier, Farnier, M., Jones, P., Severance, R., Averna, M., Steinhagen-Thiessen, E., Colhoun, H., Du, Y., Hanotin, C., and Donahue, S.

Subjects
Monoclonal antibody, medicine.medical_specialty, Time Factors, Settore MED/09 - Medicina Interna, Injections, Subcutaneous, Hypercholesterolemia, Urology, 030204 cardiovascular system & hematology, Pharmacology, Antibodies, Monoclonal, Humanized, law.invention, PCSK9, Rosuvastatin, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Ezetimibe, Randomized controlled trial, law, medicine, Clinical endpoint, Humans, Low-density lipoprotein cholesterol, In patient, 030212 general & internal medicine, Rosuvastatin Calcium, Alirocumab, Cardiology and Cardiovascular Medicine, Retrospective Studies, Dose-Response Relationship, Drug, business.industry, Anticholesteremic Agents, Antibodies, Monoclonal, nutritional and metabolic diseases, Cholesterol, LDL, Treatment Outcome, Cardiovascular Diseases, Drug Therapy, Combination, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Follow-Up Studies, medicine.drug
Abstract

OBJECTIVE: To compare lipid-lowering efficacy of adding alirocumab to rosuvastatin versus other treatment strategies (NCT01730053).METHODS: Patients receiving baseline rosuvastatin regimens (10 or 20 mg) were randomized to: add-on alirocumab 75 mg every-2-weeks (Q2W) (1-mL subcutaneous injection via pre-filled pen); add-on ezetimibe 10 mg/day; or double-dose rosuvastatin. Patients had cardiovascular disease (CVD) and low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL (1.8 mmol/L) or CVD risk factors and LDL-C ≥100 mg/dL (2.6 mmol/L). In the alirocumab group, dose was blindly increased at Week 12 to 150 mg Q2W (also 1-mL volume) in patients not achieving their LDL-C target. Primary endpoint was percent change in calculated LDL-C from baseline to 24 weeks (intent-to-treat).RESULTS: 305 patients were randomized. In the baseline rosuvastatin 10 mg group, significantly greater LDL-C reductions were observed with add-on alirocumab (-50.6%) versus ezetimibe (-14.4%; p < 0.0001) and double-dose rosuvastatin (-16.3%; p < 0.0001). In the baseline rosuvastatin 20 mg group, LDL-C reduction with add-on alirocumab was -36.3% compared with -11.0% with ezetimibe and -15.9% with double-dose rosuvastatin (p = 0.0136 and 0.0453, respectively; pre-specified threshold for significance p < 0.0125). Overall, ∼80% alirocumab patients were maintained on 75 mg Q2W. Of alirocumab-treated patients, 84.9% and 66.7% in the baseline rosuvastatin 10 and 20 mg groups, respectively, achieved risk-based LDL-C targets. Treatment-emergent adverse events occurred in 56.3% of alirocumab patients versus 53.5% ezetimibe and 67.3% double-dose rosuvastatin (pooled data).CONCLUSIONS: The addition of alirocumab to rosuvastatin provided incremental LDL-C lowering versus adding ezetimibe or doubling the rosuvastatin dose.

Published
2016
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26. Long-term maintenance of weight loss after a very-low-calorie diet: a randomized blinded trial of the efficacy and tolerability of sibutramine.

Author

Apfelbaum, Marian, Vague, Philippe, Apfelbaum, M, Vague, P, Ziegler, O, Hanotin, C, Thomas, F, and Leutenegger, E

Subjects
*APPETITE depressants, *WEIGHT loss, *LOW-calorie diet
Abstract

Background: Very-low-calorie diets are a well established method to achieve substantial short-term weight loss in obese patients, but long-term maintenance of the weight loss is very disappointing. A combined very-low-calorie diet and pharmacologic approach could be an effective means of prolonging its benefits.Patients and Methods: Eligible patients had a body-mass index greater than 30 kg/m2; those who lost 6 kg or more during a 4-week treatment with a very-low-calorie diet were randomly assigned to 1 year of treatment with sibutramine (10 mg) or identical placebo.Results: In an intention-to-treat analysis, mean (+/-SD) absolute weight change at 1 year (or study endpoint) was -5.2 (+/-7.5) kg in the 81 patients in the sibutramine group and +0.5 (+/-5.7) kg in the 78 patients in the placebo group (P = 0.004). When compared with their weight at study entry (before the very-low-calorie diet), 86% of patients in the sibutramine group had lost at least 5% of their weight, compared with only 55% of those in the placebo group (P <0.001) at the study endpoint. Similarly, at month 12, 75% of subjects in the sibutramine group maintained at least 100% of the weight loss achieved with a very-low-calorie diet, compared with 42% in the placebo group (P <0.01).Conclusion: Following a very-low-calorie diet, sibutramine is effective in maintaining and improving weight loss for up to 1 year. [ABSTRACT FROM AUTHOR]

Published
1999
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27. Antegrade embolization of varicocele with cyanoacrylate glue: a case report.

Author

Le Tat T, Jost R, Hanotin C, Lucas A, Laouisset L, Hakime A, and Kuoch V

Abstract

Background: Varicocele embolization is an effective, minimally invasive treatment option, with a symptom improvement rate of around 90%. However, anatomical variations and post-embolization recurrences pose challenges to its efficacy. This article discusses the antegrade embolization technique as a viable alternative for cases in which retrograde embolization fails, offering a broader spectrum of treatment options for varicocele., Case Presentation: This case report details the treatment of a 27-year-old male with a left varicocele, diagnosed during infertility assessment, using an alternative embolization technique. Despite initial failed attempts at retrograde catheterization via the femoral vein, a direct inguinal puncture of the left testicular vein was successfully performed under ultrasound guidance. A mixture of Glubran® and Lipiodol® was used for embolization, achieving varicocele embolization without complications. The patient was discharged 2 hours post-procedure, with follow-up confirming the procedure's effectiveness and safety., Conclusion: This article introduces a less invasive, ultrasound-guided technique for varicocele embolization, presenting a viable alternative to surgery when conventional retrograde methods fail., (© 2024. The Author(s).)

Published
2024
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28. Predictive Factors for Recurrent Hemoptysis after Bronchial Artery Embolization in Patients with Lung Cancer.

Author

Hanotin C, Salvayre R, Lassalle L, Fartoukh M, Lehrer R, Gibelin A, and Barral M

Abstract

Purpose: To identify clinical, radiological, and angiographic characteristics associated with recurrent hemoptysis after bronchial artery embolization (BAE) in patients with lung cancer and severe hemoptysis admitted to the intensive care unit (ICU)., Materials and Methods: A total of 144 consecutive patients with lung cancer who underwent BAE for life-threatening hemoptysis admitted in the ICU between 2014 and 2022 were retrospectively included. Demographics, laboratory values, clinical course, and radiological/angiographic features were compared between those with and without recurrent hemoptysis within 1 month after embolization., Results: Of the 144 patients (mean age, 60.2 years [SD ± 10.9]; females, 15.3%), 34.7% (50/144) experienced clinically relevant recurrent hemoptysis within 1 month; among them, 29 of 50 (58.0%) cases necessitated a second embolization. Massive hemoptysis was observed in 54.2%, with 16.7% receiving the vasopressin analog terlipressin. The mean volume of hemoptysis and simplified acute physiology score II (SAPS II) were 235 mL (SD ± 214.3) and 31.2 (SD ± 18.6), respectively. Computed tomography (CT) angiography revealed pulmonary artery (PA) injury (11.5%) and necrosis/cavitation (25.8%), and PA embolization was performed in 15.3% of cases. Technical success rate was 92%. SAPS II (P = .01), massive hemoptysis (P < .001), terlipressin use (P = .01), necrosis/cavitation (P = .01), and PA injury on CT angiography (P < .001) were associated with recurrent hemoptysis. Independent predictors on multivariate analysis were massive hemoptysis (P = .016) and PA injury on CT angiography (P = .001)., Conclusions: In patients with lung cancer and life-threatening hemoptysis treated by BAE, massive hemoptysis and PA injury identified on CT angiography are independent predictors of recurrent hemoptysis., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

Published
2024
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29. Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome.

Author

Bittner VA, Szarek M, Aylward PE, Bhatt DL, Diaz R, Edelberg JM, Fras Z, Goodman SG, Halvorsen S, Hanotin C, Harrington RA, Jukema JW, Loizeau V, Moriarty PM, Moryusef A, Pordy R, Roe MT, Sinnaeve P, Tsimikas S, Vogel R, White HD, Zahger D, Zeiher AM, Steg PG, and Schwartz GG

Subjects
Acute Coronary Syndrome epidemiology, Adult, Aged, Antibodies, Monoclonal, Humanized pharmacology, Cardiovascular Diseases blood, Cardiovascular Diseases drug therapy, Cardiovascular Diseases epidemiology, Cholesterol, LDL blood, Female, Humans, Male, Middle Aged, Risk Factors, Treatment Outcome, Acute Coronary Syndrome blood, Acute Coronary Syndrome drug therapy, Antibodies, Monoclonal, Humanized therapeutic use, Lipoprotein(a) antagonists & inhibitors, Lipoprotein(a) blood
Abstract

Background: Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C)., Objectives: A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE)., Methods: One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina., Results: Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081)., Conclusions: Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2020
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30. Effects of Alirocumab on Cardiovascular Events After Coronary Bypass Surgery.

Author

Goodman SG, Aylward PE, Szarek M, Chumburidze V, Bhatt DL, Bittner VA, Diaz R, Edelberg JM, Hanotin C, Harrington RA, Jukema JW, Kedev S, Letierce A, Moryusef A, Pordy R, Ramos López GA, Roe MT, Viigimaa M, White HD, Zeiher AM, Steg PG, and Schwartz GG

Subjects
Aged, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Acute Coronary Syndrome surgery, Antibodies, Monoclonal, Humanized therapeutic use, Cardiovascular Diseases prevention & control, Coronary Artery Bypass, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Postoperative Complications prevention & control
Abstract

Background: Patients with acute coronary syndrome (ACS) and history of coronary artery bypass grafting (CABG) are at high risk for recurrent cardiovascular events and death., Objectives: This study sought to determine the clinical benefit of adding alirocumab to statins in ACS patients with prior CABG in a pre-specified analysis of ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab)., Methods: Patients (n = 18,924) 1 to 12 months post-ACS with elevated atherogenic lipoprotein levels despite high-intensity statin therapy were randomized to alirocumab or placebo subcutaneously every 2 weeks. Median follow-up was 2.8 years. The primary composite endpoint of major adverse cardiovascular events (MACE) comprised coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. Patients were categorized by CABG status: no CABG (n = 16,896); index CABG after qualifying ACS, but before randomization (n = 1,025); or CABG before the qualifying ACS (n = 1,003)., Results: In each CABG category, hazard ratios (95% confidence intervals) for MACE (no CABG 0.86 [0.78 to 0.95], index CABG 0.85 [0.54 to 1.35], prior CABG 0.77 [0.61 to 0.98]) and death (0.88 [0.75 to 1.03], 0.85 [0.46 to 1.59], 0.67 [0.44 to 1.01], respectively) were consistent with the overall trial results (0.85 [0.78 to 0.93] and 0.85 [0.73 to 0.98], respectively). Absolute risk reductions (95% confidence intervals) differed across CABG categories for MACE (no CABG 1.3% [0.5% to 2.2%], index CABG 0.9% [-2.3% to 4.0%], prior CABG 6.4% [0.9% to 12.0%]) and for death (0.4% [-0.1% to 1.0%], 0.5% [-1.9% to 2.9%], and 3.6% [0.0% to 7.2%])., Conclusions: Among patients with recent ACS and elevated atherogenic lipoproteins despite intensive statin therapy, alirocumab was associated with large absolute reductions in MACE and death in those with CABG preceding the ACS event. (ODYSSEY OUTCOMES: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Published
2019
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31. Alirocumab in Patients With Polyvascular Disease and Recent Acute Coronary Syndrome: ODYSSEY OUTCOMES Trial.

Author

Jukema JW, Szarek M, Zijlstra LE, de Silva HA, Bhatt DL, Bittner VA, Diaz R, Edelberg JM, Goodman SG, Hanotin C, Harrington RA, Karpov Y, Moryusef A, Pordy R, Prieto JC, Roe MT, White HD, Zeiher AM, Schwartz GG, and Steg PG

Subjects
Aged, Cardiovascular Diseases epidemiology, Double-Blind Method, Female, Humans, Male, Middle Aged, Risk Assessment, Treatment Outcome, Vascular Diseases epidemiology, Vascular Diseases etiology, Vascular Diseases prevention & control, Acute Coronary Syndrome complications, Antibodies, Monoclonal, Humanized therapeutic use, Cardiovascular Diseases etiology, Cardiovascular Diseases prevention & control, Dyslipidemias complications, Dyslipidemias drug therapy
Abstract

Background: Patients with acute coronary syndrome (ACS) and concomitant noncoronary atherosclerosis have a high risk of major adverse cardiovascular events (MACEs) and death. The impact of lipid lowering by proprotein convertase subtilisin-kexin type 9 inhibition in such patients is undetermined., Objectives: This pre-specified analysis from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) determined whether polyvascular disease influenced risks of MACEs and death and their modification by alirocumab in patients with recent ACS and dyslipidemia despite intensive statin therapy., Methods: Patients were randomized to alirocumab or placebo 1 to 12 months after ACS. The primary MACEs endpoint was the composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint., Results: Median follow-up was 2.8 years. Of 18,924 patients, 17,370 had monovascular (coronary) disease, 1,405 had polyvascular disease in 2 beds (coronary and peripheral artery or cerebrovascular), and 149 had polyvascular disease in 3 beds (coronary, peripheral artery, cerebrovascular). With placebo, the incidence of MACEs by respective vascular categories was 10.0%, 22.2%, and 39.7%. With alirocumab, the corresponding absolute risk reduction was 1.4% (95% confidence interval [CI]: 0.6% to 2.3%), 1.9% (95% CI: -2.4% to 6.2%), and 13.0% (95% CI: -2.0% to 28.0%). With placebo, the incidence of death by respective vascular categories was 3.5%, 10.0%, and 21.8%; the absolute risk reduction with alirocumab was 0.4% (95% CI: -0.1% to 1.0%), 1.3% (95% CI: -1.8% to 4.3%), and 16.2% (95% CI: 5.5% to 26.8%)., Conclusions: In patients with recent ACS and dyslipidemia despite intensive statin therapy, polyvascular disease is associated with high risks of MACEs and death. The large absolute reductions in those risks with alirocumab are a potential benefit for these patients. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]: NCT01663402)., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2019
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32. Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial.

Author

White HD, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, Edelberg JM, Erglis A, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Lopes RD, Mahaffey KW, Moryusef A, Pordy R, Roe MT, Sritara P, Tricoci P, Zeiher AM, and Schwartz GG

Subjects
Aged, Cholesterol, LDL blood, Double-Blind Method, Female, Humans, Male, Middle Aged, Myocardial Infarction blood, Prospective Studies, Antibodies, Monoclonal, Humanized therapeutic use, Myocardial Infarction classification, Myocardial Infarction prevention & control
Abstract

Aims: The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin-kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI., Methods and Results: Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77-0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77-0.99; P = 0.032) and Type 2 (0.77, 0.61-0.97; P = 0.025), but not Type 4 MI., Conclusion: After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Published
2019
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33. Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial.

Author

Ray KK, Colhoun HM, Szarek M, Baccara-Dinet M, Bhatt DL, Bittner VA, Budaj AJ, Diaz R, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Loizeau V, Lopes RD, Moryusef A, Murin J, Pordy R, Ristic AD, Roe MT, Tuñón J, White HD, Zeiher AM, Schwartz GG, and Steg PG

Subjects
Aged, Cardiovascular Diseases blood, Diabetes Complications blood, Female, Humans, Male, Middle Aged, Antibodies, Monoclonal, Humanized therapeutic use, Cardiovascular Diseases prevention & control, Diabetes Complications prevention & control
Abstract

Background: After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1·4-1·8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes., Methods: ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1-12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1:1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0·65-1·30 mmol/L. In this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)-defined on the basis of patient history, review of medical records, or baseline HbA 1c or fasting serum glucose-and risk of new-onset diabetes among those without diabetes at baseline. The primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials.gov, number NCT01663402., Findings: At study baseline, 5444 patients (28·8%) had diabetes, 8246 (43·6%) had prediabetes, and 5234 (27·7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2·20-2·28 mmol/L), after 4 months' treatment with alirocumab (0·80 mmol/L), or after 4 months' treatment with placebo (2·25-2·28 mmol/L). In the placebo group, the incidence of the primary endpoint over a median of 2·8 years was greater in patients with diabetes (16·4%) than in those with prediabetes (9·2%) or normoglycaemia (8·5%); hazard ratio (HR) for diabetes versus normoglycaemia 2·09 (95% CI 1·78-2·46, p<0·0001) and for diabetes versus prediabetes 1·90 (1·65-2·17, p<0·0001). Alirocumab resulted in similar relative reductions in the incidence of the primary endpoint in each glycaemic category, but a greater absolute reduction in the incidence of the primary endpoint in patients with diabetes (2·3%, 95% CI 0·4 to 4·2) than in those with prediabetes (1·2%, 0·0 to 2·4) or normoglycaemia (1·2%, -0·3 to 2·7; absolute risk reduction p interaction =0·0019). Among patients without diabetes at baseline, 676 (10·1%) developed diabetes in the placebo group, compared with 648 (9·6%) in the alirocumab group; alirocumab did not increase the risk of new-onset diabetes (HR 1·00, 95% CI 0·89-1·11). HRs were 0·97 (95% CI 0·87-1·09) for patients with prediabetes and 1·30 (95% CI 0·93-1·81) for those with normoglycaemia (p interaction =0·11)., Interpretation: After a recent acute coronary syndrome, alirocumab treatment targeting an LDL cholesterol concentration of 0·65-1·30 mmol/L produced about twice the absolute reduction in cardiovascular events among patients with diabetes as in those without diabetes. Alirocumab treatment did not increase the risk of new-onset diabetes., Funding: Sanofi and Regeneron Pharmaceuticals., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Published
2019
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34. Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events: The ODYSSEY OUTCOMES Trial.

Author

Szarek M, White HD, Schwartz GG, Alings M, Bhatt DL, Bittner VA, Chiang CE, Diaz R, Edelberg JM, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Kimura T, Kiss RG, Lecorps G, Mahaffey KW, Moryusef A, Pordy R, Roe MT, Tricoci P, Xavier D, Zeiher AM, and Steg PG

Subjects
Aged, Antibodies, Monoclonal, Humanized, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Male, Middle Aged, Acute Coronary Syndrome drug therapy, Antibodies, Monoclonal therapeutic use
Abstract

Background: The ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial compared alirocumab with placebo, added to high-intensity or maximum-tolerated statin treatment, after acute coronary syndrome (ACS) in 18,924 patients. Alirocumab reduced the first occurrence of the primary composite endpoint and was associated with fewer all-cause deaths., Objectives: This pre-specified analysis determined the extent to which alirocumab reduced total (first and subsequent) nonfatal cardiovascular events and all-cause deaths in ODYSSEY OUTCOMES., Methods: Hazard functions for total nonfatal cardiovascular events (myocardial infarction, stroke, ischemia-driven coronary revascularization, and hospitalization for unstable angina or heart failure) and death were jointly estimated, linked by a shared frailty accounting for patient risk heterogeneity and correlated within-patient nonfatal events. An association parameter also quantified the strength of the linkage between risk of nonfatal events and death. The model provides accurate relative estimates of nonfatal event risk if nonfatal events are associated with increased risk for death., Results: With 3,064 first and 5,425 total events, 190 fewer first and 385 fewer total nonfatal cardiovascular events or deaths were observed with alirocumab compared with placebo. Alirocumab reduced total nonfatal cardiovascular events (hazard ratio: 0.87; 95% confidence interval: 0.82 to 0.93) and death (hazard ratio: 0.83; 95% confidence interval: 0.71 to 0.97) in the presence of a strong association between nonfatal and fatal event risk., Conclusions: In patients with ACS, the total number of nonfatal cardiovascular events and deaths prevented with alirocumab was twice the number of first events prevented. Consequently, total event reduction is a more comprehensive metric to capture the totality of alirocumab clinical efficacy after ACS., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2019
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35. Relationship Between Low-Density Lipoprotein Cholesterol, Free Proprotein Convertase Subtilisin/Kexin Type 9, and Alirocumab Levels After Different Lipid-Lowering Strategies.

Author

Rey J, Poitiers F, Paehler T, Brunet A, DiCioccio AT, Cannon CP, Surks HK, Pinquier JL, Hanotin C, and Sasiela WJ

Subjects
Administration, Oral, Adolescent, Adult, Aged, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal pharmacokinetics, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Humanized, Anticholesteremic Agents administration & dosage, Anticholesteremic Agents pharmacokinetics, Anticholesteremic Agents therapeutic use, Double-Blind Method, Drug Therapy, Combination, Ezetimibe administration & dosage, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Hypercholesterolemia blood, Hypolipidemic Agents administration & dosage, Male, Middle Aged, Proprotein Convertase 9 drug effects, Young Adult, Antibodies, Monoclonal pharmacology, Anticholesteremic Agents pharmacology, Cholesterol, LDL metabolism, Fenofibrate administration & dosage, Hypercholesterolemia drug therapy, Proprotein Convertase 9 metabolism
Abstract

Background: Alirocumab undergoes target-mediated clearance via binding of proprotein convertase subtilisin/kexin type 9 (PCSK9). Statins increase PCSK9 levels; the effects of nonstatin lipid-lowering therapies are unclear. Every-4-weeks dosing of alirocumab may be appropriate for some patients in absence of background statin but is not yet approved., Methods and Results: Low-density lipoprotein cholesterol (LDL-C), PCSK9, and alirocumab levels were assessed in subjects (LDL-C >130 mg/dL, n=24/group) after a 4-week run-in taking oral ezetimibe, fenofibrate, or ezetimibe placebo, when alirocumab 150 mg every 4 weeks (days 1, 29, and 57) was added. Maximal mean LDL-C reductions from day -1 baseline (prealirocumab) occurred on day 71 in all groups: alirocumab plus placebo, 47.4%; alirocumab plus ezetimibe, 56.6%; and alirocumab plus fenofibrate, 54.3%. LDL-C reductions were sustained through day 85 with alirocumab plus placebo (47.0%); the duration of effect was slightly diminished at day 85 versus day 71 with ezetimibe (49.6%) or fenofibrate combinations (43.2%). Free PCSK9 concentrations were lowest at day 71 in all groups, then increased over time; by day 85, free PCSK9 concentrations were higher, and alirocumab levels lower, with alirocumab plus fenofibrate, and to a lesser extent alirocumab plus ezetimibe, versus alirocumab plus placebo., Conclusions: Alirocumab 150 mg every 4 weeks produced maximal LDL-C reductions of 47% in combination with placebo and 54% to 57% in combination with ezetimibe or fenofibrate. The oral lipid-lowering therapies appear to increase PCSK9 levels, leading to increased alirocumab clearance. Although the duration of effect was modestly diminished with alirocumab plus ezetimibe/fenofibrate versus placebo, the effect was less than observed in trials with background statins, and it would not preclude the use of alirocumab every 4 weeks in patients taking these nonstatin lipid-lowering therapies concomitantly., Clinical Trial Registration: URL: http://www.Clinicaltrials.gov. Unique identifier: NCT01723735., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Published
2016
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36. Effect of alirocumab on specific lipoprotein non-high-density lipoprotein cholesterol and subfractions as measured by the vertical auto profile method: analysis of 3 randomized trials versus placebo.

Author

Toth PP, Hamon SC, Jones SR, Martin SS, Joshi PH, Kulkarni KR, Banerjee P, Hanotin C, Roth EM, and McKenney JM

Subjects
Adult, Antibodies, Monoclonal, Humanized, Cholesterol, LDL, Double-Blind Method, Female, Humans, Hypercholesterolemia blood, Hypercholesterolemia drug therapy, Lipid Metabolism drug effects, Lipoproteins, HDL blood, Lipoproteins, VLDL blood, Male, Middle Aged, Randomized Controlled Trials as Topic, Triglycerides blood, Antibodies, Monoclonal therapeutic use, Lipoproteins blood
Abstract

Background: The effect of alirocumab on potentially atherogenic lipoprotein subfractions was assessed in a post hoc analysis using the vertical auto profile (VAP) method., Methods: Patients from three Phase II studies with low-density lipoprotein cholesterol (LDL-C) ≥ 2.59 mmol/L (100 mg/dL) at baseline on stable statin therapy were randomised to receive subcutaneous alirocumab 50-150 mg every 2 weeks (Q2W) or 150-300 mg every 4 weeks (according to study) or placebo for 8-12 weeks. Samples from patients treated with alirocumab 150 mg Q2W (n = 74; dose common to all three trials) or placebo (n = 71) were analysed by VAP. Percent change in lipoprotein subfractions with alirocumab vs. placebo was analysed at Weeks 6, 8 or 12 using analysis of covariance., Results: Alirocumab significantly reduced LDL-C and the cholesterol content of subfractions LDL1, LDL2 and LDL3+4. Significant reductions were also observed in triglycerides, apolipoproteins CII and CIII and the cholesterol content of very low-density, intermediate-density, and remnant lipoproteins., Conclusion: Alirocumab achieved reductions across a spectrum of atherogenic lipoproteins in patients receiving background statin therapy., Trial Registration: Clinicaltrials.gov identifiers: NCT01288443, NCT01288469, NCT01266876.

Published
2016
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37. Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patients: The ODYSSEY OPTIONS II randomized trial.

Author

Farnier M, Jones P, Severance R, Averna M, Steinhagen-Thiessen E, Colhoun HM, Du Y, Hanotin C, and Donahue S

Subjects
Antibodies, Monoclonal, Humanized, Anticholesteremic Agents administration & dosage, Cardiovascular Diseases blood, Cholesterol, LDL drug effects, Dose-Response Relationship, Drug, Double-Blind Method, Drug Therapy, Combination, Follow-Up Studies, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage, Hypercholesterolemia blood, Injections, Subcutaneous, Retrospective Studies, Time Factors, Treatment Outcome, Antibodies, Monoclonal administration & dosage, Cardiovascular Diseases prevention & control, Cholesterol, LDL blood, Ezetimibe administration & dosage, Hypercholesterolemia drug therapy, Rosuvastatin Calcium administration & dosage
Abstract

Objective: To compare lipid-lowering efficacy of adding alirocumab to rosuvastatin versus other treatment strategies (NCT01730053)., Methods: Patients receiving baseline rosuvastatin regimens (10 or 20 mg) were randomized to: add-on alirocumab 75 mg every-2-weeks (Q2W) (1-mL subcutaneous injection via pre-filled pen); add-on ezetimibe 10 mg/day; or double-dose rosuvastatin. Patients had cardiovascular disease (CVD) and low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL (1.8 mmol/L) or CVD risk factors and LDL-C ≥100 mg/dL (2.6 mmol/L). In the alirocumab group, dose was blindly increased at Week 12 to 150 mg Q2W (also 1-mL volume) in patients not achieving their LDL-C target. Primary endpoint was percent change in calculated LDL-C from baseline to 24 weeks (intent-to-treat)., Results: 305 patients were randomized. In the baseline rosuvastatin 10 mg group, significantly greater LDL-C reductions were observed with add-on alirocumab (-50.6%) versus ezetimibe (-14.4%; p < 0.0001) and double-dose rosuvastatin (-16.3%; p < 0.0001). In the baseline rosuvastatin 20 mg group, LDL-C reduction with add-on alirocumab was -36.3% compared with -11.0% with ezetimibe and -15.9% with double-dose rosuvastatin (p = 0.0136 and 0.0453, respectively; pre-specified threshold for significance p < 0.0125). Overall, ∼80% alirocumab patients were maintained on 75 mg Q2W. Of alirocumab-treated patients, 84.9% and 66.7% in the baseline rosuvastatin 10 and 20 mg groups, respectively, achieved risk-based LDL-C targets. Treatment-emergent adverse events occurred in 56.3% of alirocumab patients versus 53.5% ezetimibe and 67.3% double-dose rosuvastatin (pooled data)., Conclusions: The addition of alirocumab to rosuvastatin provided incremental LDL-C lowering versus adding ezetimibe or doubling the rosuvastatin dose., (Copyright © 2015 Regeneron Pharmaceuticals, Inc. Published by Elsevier Ireland Ltd.. All rights reserved.)

Published
2016
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38. Effect of PCSK9 Inhibition by Alirocumab on Lipoprotein Particle Concentrations Determined by Nuclear Magnetic Resonance Spectroscopy.

Author

Koren MJ, Kereiakes D, Pourfarzib R, Winegar D, Banerjee P, Hamon S, Hanotin C, and McKenney JM

Subjects
Adult, Aged, Antibodies, Monoclonal, Humanized, Atorvastatin therapeutic use, Biomarkers blood, Cholesterol, LDL blood, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Hypercholesterolemia blood, Hypercholesterolemia diagnosis, Hypercholesterolemia enzymology, Lipoproteins, HDL blood, Lipoproteins, VLDL blood, Male, Middle Aged, Particle Size, Proprotein Convertase 9, Proprotein Convertases metabolism, Serine Endopeptidases metabolism, Treatment Outcome, Antibodies, Monoclonal therapeutic use, Hypercholesterolemia drug therapy, Hypolipidemic Agents therapeutic use, Lipoproteins blood, Nuclear Magnetic Resonance, Biomolecular, Proprotein Convertases antagonists & inhibitors, Serine Proteinase Inhibitors therapeutic use
Abstract

Background: In patients with discordance between low-density lipoprotein (LDL) cholesterol and LDL particle (LDL-P) concentrations, cardiovascular risk more closely correlates with LDL-P., Methods and Results: We investigated the effect of alirocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9, on lipoprotein particle concentration and size in hypercholesterolemic patients, using nuclear magnetic resonance spectroscopy. Plasma samples were collected from patients receiving alirocumab 150 mg every 2 weeks (n=26) or placebo (n=31) during a phase II, double-blind, placebo-controlled trial in patients (LDL cholesterol ≥100 mg/dL) on a stable atorvastatin dose. In this post hoc analysis, percentage change in concentrations of LDL-P, very-low-density lipoprotein particles, and high-density lipoprotein particles from baseline to week 12 was determined by nuclear magnetic resonance. Alirocumab significantly reduced mean concentrations of total LDL-P (-63.3% versus -1.0% with placebo) and large (-71.3% versus -21.8%) and small (-54.0% versus +17.8%) LDL-P subfractions and total very-low-density lipoprotein particle concentrations (-36.4% versus +33.4%; all P<0.01). Total high-density lipoprotein particles increased with alirocumab (+11.2% versus +1.4% with placebo; P<0.01). There were greater increases in large (44.6%) versus medium (17.7%) or small high-density lipoprotein particles (2.8%) with alirocumab. LDL-P size remained relatively unchanged in both groups; however, very-low-density and high-density lipoprotein particle sizes increased to a significantly greater extent with alirocumab., Conclusions: Alirocumab significantly reduced LDL-C and LDL-P concentrations in hypercholesterolemic patients receiving stable atorvastatin therapy. These findings may be of particular relevance to patients with discordant LDL-C and LDL-P concentrations., Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT01288443., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Published
2015
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39. Alirocumab as Add-On to Atorvastatin Versus Other Lipid Treatment Strategies: ODYSSEY OPTIONS I Randomized Trial.

Author

Bays H, Gaudet D, Weiss R, Ruiz JL, Watts GF, Gouni-Berthold I, Robinson J, Zhao J, Hanotin C, and Donahue S

Subjects
Aged, Antibodies blood, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal immunology, Antibodies, Monoclonal, Humanized, Anticholesteremic Agents adverse effects, Anticholesteremic Agents immunology, Atorvastatin, Azetidines administration & dosage, Azetidines adverse effects, Azetidines immunology, Cardiovascular Diseases blood, Cholesterol, LDL blood, Drug Therapy, Combination, Ezetimibe, Female, Heptanoic Acids adverse effects, Heptanoic Acids immunology, Humans, Male, Middle Aged, Pyrroles adverse effects, Pyrroles immunology, Treatment Outcome, Antibodies, Monoclonal administration & dosage, Anticholesteremic Agents administration & dosage, Cardiovascular Diseases prevention & control, Heptanoic Acids administration & dosage, Pyrroles administration & dosage
Abstract

Context: Despite current standard of care, many patients at high risk of cardiovascular disease (CVD) still have elevated low-density lipoprotein cholesterol (LDL-C) levels. Alirocumab is a fully human monoclonal antibody inhibitor of proprotein convertase subtilisin/kexin type 9., Objective: The objective of the study was to compare the LDL-C-lowering efficacy of adding alirocumab vs other common lipid-lowering strategies., Design, Patients, and Interventions: Patients (n = 355) with very high CVD risk and LDL-C levels of 70 mg/dL or greater or high CVD risk and LDL-C of 100 mg/dL or greater on baseline atorvastatin 20 or 40 mg were randomized to one of the following: 1) add-on alirocumab 75 mg every 2 weeks (Q2W) sc; 2) add-on ezetimibe 10 mg/d; 3) double atorvastatin dose; or 4) for atorvastatin 40 mg regimen only, switch to rosuvastatin 40 mg. For patients not achieving protocol-defined LDL-C goals, the alirocumab dose was increased (blinded) at week 12 to 150 mg Q2W., Main Outcome Measure: The primary end point was percentage change in calculated LDL-C from baseline to 24 weeks (intent to treat)., Results: Among atorvastatin 20 and 40 mg regimens, respectively, add-on alirocumab reduced LDL-C levels by 44.1% and 54.0% (P < .001 vs all comparators); add-on ezetimibe, 20.5% and 22.6%; doubling of atorvastatin dose, 5.0% and 4.8%; and switching atorvastatin 40 mg to rosuvastatin 40 mg, 21.4%. Most alirocumab-treated patients (87.2% and 84.6%) achieved their LDL-C goals. Most alirocumab-treated patients (86%) maintained their 75-mg Q2W regimen. Treatment-emergent adverse events occurred in 65.4% of alirocumab patients vs 64.4% ezetimibe and 63.8% double atorvastatin/switch to rosuvastatin (data were pooled)., Conclusions: Adding alirocumab to atorvastatin provided significantly greater LDL-C reductions vs adding ezetimibe, doubling atorvastatin dose, or switching to rosuvastatin and enabled greater LDL-C goal achievement.

Published
2015
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40. Safety and efficacy of alirocumab 150 mg every 2 weeks, a fully human proprotein convertase subtilisin/kexin type 9 monoclonal antibody: A Phase II pooled analysis.

Author

Koren MJ, Roth EM, McKenney JM, Gipe D, Hanotin C, Ferrand AC, Wu R, and Dufour R

Subjects
Antibodies, Monoclonal, Humanized, Cholesterol, LDL blood, Clinical Trials, Phase II as Topic, Humans, Randomized Controlled Trials as Topic, Treatment Outcome, Antibodies, Monoclonal administration & dosage, Anticholesteremic Agents administration & dosage, Hypercholesterolemia drug therapy
Abstract

Background: Alirocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9, is in Phase III development for the treatment of hypercholesterolemia. In Phase II studies, 150 mg every 2 weeks (Q2W) was the highest Q2W dose studied, and it is currently the highest Q2W dose under development. To better assess the safety and efficacy of this dose, data across three Phase II studies were pooled., Methods: We analyzed data from three double-blind, randomized, placebo-controlled Phase II studies of 8 or 12 weeks' duration. In the current analysis, 77 patients were randomized to the control group and 108 were randomized to alirocumab 150 mg Q2W administered via a single 1 mL subcutaneous injection., Results: Adverse events (AEs) occurred in 58.3% of alirocumab patients compared with 54.5% of placebo-controlled patients. The most common AE was mild, transient injection-site reactions. No signal for muscle symptoms such as myalgia and no cases of neurocognitive effects were reported or observed. One alirocumab patient, also receiving atorvastatin 80 mg/day, had an increase in aspartate transaminase 3 to 5 times the upper limit of normal. Alirocumab 150 mg Q2W reduced low-density lipoprotein cholesterol (LDL-C) from baseline by 68.4% compared with 10.5% for the control group. More than 90% of patients achieved an LDL-C target of < 70 mg/dL with alirocumab versus 8% with control. Marked reductions in other atherogenic lipids and modest increases in high-density lipoprotein cholesterol were also observed., Conclusion: At the highest Q2W dose under development (150 mg), alirocumab appears well tolerated and produces robust LDL-C reductions. These data suggest that alirocumab 150 mg Q2W is an appropriate dose for further evaluation in Phase III trials.

Published
2015
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41. A randomized study of the relative pharmacokinetics, pharmacodynamics, and safety of alirocumab, a fully human monoclonal antibody to PCSK9, after single subcutaneous administration at three different injection sites in healthy subjects.

Author

Lunven C, Paehler T, Poitiers F, Brunet A, Rey J, Hanotin C, and Sasiela WJ

Subjects
Adult, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal pharmacology, Antibodies, Monoclonal, Humanized, Cholesterol, LDL blood, Female, Humans, Injections, Subcutaneous, Male, Middle Aged, Proprotein Convertase 9, Proprotein Convertases blood, Serine Endopeptidases blood, Antibodies, Monoclonal pharmacokinetics, Proprotein Convertases antagonists & inhibitors
Abstract

Aims: We investigated the relative pharmacokinetics, pharmacodynamics, and safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab following injection at three different sites., Methods: Sixty healthy subjects (39 male, 21 female; age 20-45 years) were randomized to receive a single subcutaneous injection of alirocumab 75 mg via 1-mL prefilled pen into the abdomen, upper arm, or thigh (NCT01785329). Subjects were followed for 85 days ± 2 days following study drug administration. Pharmacokinetic (PK) parameters for the systemic exposure of alirocumab were calculated, and levels of free PCSK9 were assessed. Percentage changes from baseline in LDL-C were compared between injection site groups using linear mixed-effects models., Results: Alirocumab concentration-time profiles were similar, and free PCSK9 levels were reduced to approximately zero between Day 3 and Day 4 postinjection in all groups. LDL-C levels reached nadir on Day 15 postinjection in all groups with mean percentage reductions of 48.4% (abdomen), 39.5% (upper arm), and 45.6% (thigh) at this time point. A similar effect on LDL-C levels was seen across the entire time course of the study at all three injection sites. Treatment-emergent adverse events were experienced by 8/20 (abdomen), 11/20 (upper arm), and 13/20 (thigh) subjects. There were 2 mild/transient injection site reactions. There were no serious adverse events., Discussion: A single subcutaneous administration of alirocumab 75 mg via prefilled pen was well tolerated with similar pharmacokinetics and pharmacodynamics when injected into the abdomen, upper arm, or thigh., Conclusion: These results suggest that alirocumab can be interchangeably injected in the abdomen, upper arm, or thigh., (© 2014 Sanofi and Regeneron Pharmaceuticals Inc. Cardiovascular Therapeutics published by John Wiley & Sons Ltd.)

Published
2014
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42. Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial.

Author

Schwartz GG, Bessac L, Berdan LG, Bhatt DL, Bittner V, Diaz R, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Mahaffey KW, Moryusef A, Pordy R, Roe MT, Rorick T, Sasiela WJ, Shirodaria C, Szarek M, Tamby JF, Tricoci P, White H, Zeiher A, and Steg PG

Subjects
Acute Coronary Syndrome complications, Antibodies, Monoclonal, Humanized, Apolipoproteins B blood, Atorvastatin, Cholesterol, LDL blood, Double-Blind Method, Drug Therapy, Combination, Fluorobenzenes therapeutic use, Heptanoic Acids therapeutic use, Hospitalization, Humans, Hypercholesterolemia complications, Proprotein Convertase 9, Pyrimidines therapeutic use, Pyrroles therapeutic use, Rosuvastatin Calcium, Serine Endopeptidases, Sulfonamides therapeutic use, Treatment Outcome, Acute Coronary Syndrome drug therapy, Angina, Unstable prevention & control, Antibodies, Monoclonal therapeutic use, Anticholesteremic Agents therapeutic use, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Hypercholesterolemia drug therapy, Myocardial Infarction prevention & control, Proprotein Convertases antagonists & inhibitors, Stroke prevention & control
Abstract

Background: Following acute coronary syndrome (ACS), the risk for future cardiovascular events is high and is related to levels of low-density lipoprotein cholesterol (LDL-C) even within the setting of intensive statin treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates LDL receptor expression and circulating levels of LDL-C. Antibodies to PCSK9 can produce substantial and sustained reductions of LDL-C. The ODYSSEY Outcomes trial tests the hypothesis that treatment with alirocumab, a fully human monoclonal antibody to PCSK9, improves cardiovascular outcomes after ACS., Design: This Phase 3 study will randomize approximately 18,000 patients to receive biweekly injections of alirocumab (75-150 mg) or matching placebo beginning 1 to 12 months after an index hospitalization for acute myocardial infarction or unstable angina. Qualifying patients are treated with atorvastatin 40 or 80 mg daily, rosuvastatin 20 or 40 mg daily, or the maximum tolerated and approved dose of one of these agents and fulfill one of the following criteria: LDL-C ≥ 70 mg/dL, non-high-density lipoprotein cholesterol ≥ 100 mg/dL, or apolipoprotein B ≥ 80 mg/dL. The primary efficacy measure is time to first occurrence of coronary heart disease death, acute myocardial infarction, hospitalization for unstable angina, or ischemic stroke. The trial is expected to continue until 1613 primary end point events have occurred with minimum follow-up of at least 2 years, providing 90% power to detect a 15% hazard reduction. Adverse events of special interest include allergic events and injection site reactions. Interim analyses are planned when approximately 50% and 75% of the targeted number of primary end points have occurred., Summary: ODYSSEY Outcomes will determine whether the addition of the PCSK9 antibody alirocumab to intensive statin therapy reduces cardiovascular morbidity and mortality after ACS., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2014
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43. Efficacy and safety of alirocumab as add-on therapy in high-cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg): design and rationale of the ODYSSEY OPTIONS Studies.

Author

Robinson JG, Colhoun HM, Bays HE, Jones PH, Du Y, Hanotin C, and Donahue S

Subjects
Antibodies, Monoclonal, Humanized, Atorvastatin, Cardiovascular Diseases etiology, Cholesterol, LDL blood, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Humans, Hypercholesterolemia complications, Male, Rosuvastatin Calcium, Treatment Outcome, Antibodies, Monoclonal administration & dosage, Anticholesteremic Agents therapeutic use, Cardiovascular Diseases prevention & control, Fluorobenzenes therapeutic use, Heptanoic Acids therapeutic use, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Hypercholesterolemia drug therapy, Pyrimidines therapeutic use, Pyrroles therapeutic use, Sulfonamides therapeutic use
Abstract

The phase 3 ODYSSEY OPTIONS studies (OPTIONS I, NCT01730040; OPTIONS II, NCT01730053) are multicenter, multinational, randomized, double-blind, active-comparator, 24-week studies evaluating the efficacy and safety of alirocumab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, as add-on therapy in ∼ 650 high-cardiovascular (CV)-risk patients whose low-density lipoprotein cholesterol (LDL-C) levels are ≥100 mg/dL or ≥70 mg/dL according to the CV-risk category, high and very high CV risk, respectively, with atorvastatin (20-40 mg/d) or rosuvastatin (10-20 mg/d). Patients are randomized to receive alirocumab 75 mg via a single, subcutaneous, 1-mL injection by prefilled pen every 2 weeks (Q2W) as add-on therapy to atorvastatin (20-40 mg) or rosuvastatin (10-20 mg); or to receive ezetimibe 10 mg/d as add-on therapy to statin; or to receive statin up-titration; or to switch from atorvastatin to rosuvastatin (OPTIONS I only). At week 12, based on week 8 LDL-C levels, the alirocumab dose may be increased from 75 mg to 150 mg Q2W if LDL-C levels remain ≥100 mg/dL or ≥70 mg/dL in patients with high or very high CV risk, respectively. The primary efficacy endpoint in both studies is difference in percent change in calculated LDL-C from baseline to week 24 in the alirocumab vs control arms. The studies may provide guidance to inform clinical decision-making when patients with CV risk require additional lipid-lowering therapy to further reduce LDL-C levels. The flexibility of the alirocumab dosing regimen allows for individualized therapy based on the degree of LDL-C reduction required to achieve the desired LDL-C level., (© 2014 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

Published
2014
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44. Effect of alirocumab, a monoclonal proprotein convertase subtilisin/kexin 9 antibody, on lipoprotein(a) concentrations (a pooled analysis of 150 mg every two weeks dosing from phase 2 trials).

Author

Gaudet D, Kereiakes DJ, McKenney JM, Roth EM, Hanotin C, Gipe D, Du Y, Ferrand AC, Ginsberg HN, and Stein EA

Subjects
Antibodies, Monoclonal, Humanized, Atorvastatin, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Drug Therapy, Combination, Female, Follow-Up Studies, Heptanoic Acids administration & dosage, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage, Male, Middle Aged, Nephelometry and Turbidimetry, Pyrroles administration & dosage, Steroid Metabolism, Inborn Errors blood, Subtilisin immunology, Time Factors, Treatment Outcome, Antibodies, Monoclonal administration & dosage, Cholic Acids blood, Lipoprotein(a) blood, Steroid Metabolism, Inborn Errors drug therapy
Abstract

Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease, with limited treatment options. This analysis evaluated the effect of a monoclonal antibody to proprotein convertase subtilisin/kexin 9, alirocumab 150 mg every 2 weeks (Q2W), on Lp(a) levels in pooled data from 3 double-blind, randomized, placebo-controlled, phase 2 studies of 8 or 12 weeks' duration conducted in patients with hypercholesterolemia on background lipid-lowering therapy (NCT01266876, NCT01288469, and NCT01288443). Data were available for 102 of 108 patients who received alirocumab 150 mg Q2W and 74 of 77 patients who received placebo. Alirocumab resulted in a significant reduction in Lp(a) from baseline compared with placebo (-30.3% vs -0.3%, p <0.0001). Median percentage Lp(a) reductions in the alirocumab group were of a similar magnitude across a range of baseline Lp(a) levels, resulting in greater absolute reductions in Lp(a) in patients with higher baseline levels. Regression analysis indicated that <5% of the variance in the reduction of Lp(a) was explained by the effect of alirocumab on low-density lipoprotein cholesterol. In conclusion, pooled data from 3 phase 2 trials demonstrate substantive reduction in Lp(a) with alirocumab 150 mg Q2W, including patients with baseline Lp(a) >50 mg/dl. Reductions in Lp(a) only weakly correlated with the magnitude of low-density lipoprotein cholesterol lowering., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2014
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45. Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia.

Author

Roth EM, McKenney JM, Hanotin C, Asset G, and Stein EA

Subjects
Aged, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal, Humanized, Atorvastatin, Cholesterol, LDL blood, Drug Therapy, Combination, Female, Heptanoic Acids administration & dosage, Heptanoic Acids adverse effects, Humans, Least-Squares Analysis, Male, Middle Aged, Proprotein Convertase 9, Pyrroles administration & dosage, Pyrroles adverse effects, Serine Endopeptidases, Treatment Outcome, Antibodies, Monoclonal therapeutic use, Heptanoic Acids therapeutic use, Hypercholesterolemia drug therapy, Proprotein Convertases antagonists & inhibitors, Pyrroles therapeutic use
Abstract

Background: Serum proprotein convertase subtilisin/kexin 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, increasing the degradation of LDL receptors and reducing the rate at which LDL cholesterol is removed from the circulation. REGN727/SAR236553 (designated here as SAR236553), a fully human PCSK9 monoclonal antibody, increases the recycling of LDL receptors and reduces LDL cholesterol levels., Methods: We performed a phase 2, multicenter, double-blind, placebo-controlled trial involving 92 patients who had LDL cholesterol levels of 100 mg per deciliter (2.6 mmol per liter) or higher after treatment with 10 mg of atorvastatin for at least 7 weeks. Patients were randomly assigned to receive 8 weeks of treatment with 80 mg of atorvastatin daily plus SAR236553 once every 2 weeks, 10 mg of atorvastatin daily plus SAR236553 once every 2 weeks, or 80 mg of atorvastatin daily plus placebo once every 2 weeks and were followed for an additional 8 weeks after treatment., Results: The least-squares mean (±SE) percent reduction from baseline in LDL cholesterol was 73.2±3.5 with 80 mg of atorvastatin plus SAR236553, as compared with 17.3±3.5 with 80 mg of atorvastatin plus placebo (P<0.001) and 66.2±3.5 with 10 mg of atorvastatin plus SAR236553. All the patients who received SAR236553, as compared with 52% of those who received 80 mg of atorvastatin plus placebo, attained an LDL cholesterol level of less than 100 mg per deciliter, and at least 90% of the patients who received SAR236553, as compared with 17% who received 80 mg of atorvastatin plus placebo, attained LDL cholesterol levels of less than 70 mg per deciliter (1.8 mmol per liter)., Conclusions: In a randomized trial involving patients with primary hypercholesterolemia, adding SAR236553 to either 10 mg of atorvastatin or 80 mg of atorvastatin resulted in a significantly greater reduction in LDL cholesterol than that attained with 80 mg of atorvastatin alone. (Funded by Sanofi and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT01288469.).

Published
2012
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46. Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy.

Author

McKenney JM, Koren MJ, Kereiakes DJ, Hanotin C, Ferrand AC, and Stein EA

Subjects
Adult, Aged, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal, Humanized, Anticholesteremic Agents administration & dosage, Anticholesteremic Agents adverse effects, Atorvastatin, Double-Blind Method, Drug Synergism, Female, Humans, Hypercholesterolemia blood, Male, Middle Aged, Proprotein Convertase 9, Proprotein Convertases metabolism, Serine Endopeptidases metabolism, Time Factors, Treatment Outcome, Antibodies, Monoclonal therapeutic use, Anticholesteremic Agents therapeutic use, Cholesterol, LDL blood, Heptanoic Acids administration & dosage, Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage, Hypercholesterolemia drug therapy, Proprotein Convertases antagonists & inhibitors, Pyrroles administration & dosage
Abstract

Objectives: The primary objective of this study was to evaluate the low-density lipoprotein cholesterol (LDL-C)-lowering efficacy of 5 SAR236553/REGN727 (SAR236553) dosing regimens versus placebo at week 12 in patients with LDL-C ≥100 mg/dl on stable atorvastatin therapy. Secondary objectives included evaluation of effects on other lipid parameters and the attainment of LDL-C treatment goals of <100 mg/dl (2.59 mmol/l) and <70 mg/dl (1.81 mmol/l)., Background: Serum proprotein convertase subtilisin kexin 9 (PCSK9) binds to low-density lipoprotein receptors, increasing serum LDL-C. SAR236553 is a fully human monoclonal antibody to PCSK9., Methods: This double-blind, parallel-group, placebo-controlled trial randomized 183 patients with LDL-C ≥100 mg/dl (2.59 mmol/l) on stable-dose atorvastatin 10, 20, or 40 mg for ≥6 weeks to: subcutaneous placebo every 2 weeks (Q2W); SAR236553 50, 100, or 150 mg Q2W; or SAR236553 200 or 300 mg every 4 weeks (Q4W), alternating with placebo for a total treatment period of 12 weeks., Results: SAR236553 demonstrated a clear dose-response relationship with respect to percentage LDL-C lowering for both Q2W and Q4W administration: 40%, 64%, and 72% with 50, 100, and 150 mg Q2W, respectively, and 43% and 48% with 200 and 300 mg Q4W. LDL-C reduction with placebo at week 12 was 5%. SAR236553 also substantially reduced non-high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a). SAR236553 was generally well tolerated. One patient on SAR236553 experienced a serious adverse event of leukocytoclastic vasculitis., Conclusions: When added to atorvastatin, PCSK9 inhibition with SAR236553 further reduces LDL-C by 40% to 72%. These additional reductions are both dose- and dosing frequency-dependent. (Efficacy and Safety Evaluation of SAR236553 [REGN727] in Patients With Primary Hypercholesterolemia and LDL-cholesterol on Stable Atorvastatin Therapy; NCT01288443)., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Published
2012
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47. Long-term effect of CB1 blockade with rimonabant on cardiometabolic risk factors: two year results from the RIO-Europe Study.

Author

Van Gaal LF, Scheen AJ, Rissanen AM, Rössner S, Hanotin C, and Ziegler O

Subjects
Adult, Anti-Obesity Agents adverse effects, Blood Glucose metabolism, Body Mass Index, Cardiovascular Diseases etiology, Cholesterol, HDL blood, Dose-Response Relationship, Drug, Epidemiologic Methods, Female, Humans, Insulin blood, Male, Metabolic Syndrome prevention & control, Middle Aged, Obesity blood, Obesity physiopathology, Piperidines adverse effects, Pyrazoles adverse effects, Rimonabant, Treatment Outcome, Triglycerides blood, Weight Loss drug effects, Anti-Obesity Agents therapeutic use, Cannabinoid Receptor Antagonists, Cardiovascular Diseases prevention & control, Obesity drug therapy, Piperidines therapeutic use, Pyrazoles therapeutic use
Abstract

Aims: Rimonabant, the first selective cannabinoid type 1 receptor blocker, has been shown to produce weight loss and improvements in several cardiometabolic risk factors over 1 year. We report the 2 year efficacy and tolerability data of rimonabant., Methods and Results: Patients with a body mass index > or =30 or >27 kg/m(2) with treated/untreated hypertension, dyslipidaemia, or both, were randomized to double-blind treatment with placebo, rimonabant 5 or 20 mg once daily plus a calorie-restricted diet for 2 years. Weight loss from baseline to 2 years in the intention-to-treat population was significantly greater with rimonabant 20 mg (mean +/- SD: -5.5 +/- 7.7 kg; P < 0.001) and 5 mg (-2.9 +/- 6.5 kg; P = 0.002) than placebo (-1.2 +/- 6.8 kg). Rimonabant 20 mg produced significantly greater improvements than placebo in waist circumference, high-density lipoprotein cholesterol, triglycerides, fasting glucose and insulin levels, insulin resistance, and metabolic syndrome prevalence. Rimonabant 20 mg produced clinically meaningful improvements in all Impact of Weight on Quality of Life-Lite questionnaire domain scores at 2 years. Rimonabant was generally well tolerated and rates of adverse events, including depressed mood disorders and disturbances were similar to placebo during year 2. Proportions of patients with clinically significant depression (Hospital Anxiety and Depression Scale score >11) were similar in all treatment groups., Conclusion: Rimonabant 20 mg over 2 years promoted clinically relevant and durable weight loss and improvements in cardiometabolic risk factors.

Published
2008
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48. [Rimonabant improves cardiometabolic risk profile in obese or overweight subjects: overview of RIO studies].

Author

Scheen AJ, Van Gaal LG, Després JP, Pi-Sunyer X, Golay A, and Hanotin C

Subjects
Cannabinoid Receptor Antagonists, Humans, Randomized Controlled Trials as Topic, Rimonabant, Anti-Obesity Agents therapeutic use, Metabolic Syndrome prevention & control, Obesity drug therapy, Overweight drug effects, Piperidines therapeutic use, Pyrazoles therapeutic use
Abstract

RIO (Rimonabant In Obesity and related disorders) is a large phase 3 programme (>6600 patients) evaluating the efficacy and safety of rimonabant (5 or 20 mg/day), a CBI receptor antagonist of endocannabinoid system, in obese or overweight patients with or without comorbidities (RIO-Europe and RIO-North America), with untreated dyslipidaemia (RIO-Lipids) or with type 2 diabetes treated with metformin or sulfonylurea (RIO-Diabetes). Compared to placebo, rimonabant 20 mg/day consistently increases weight loss, reduces waist circumference, increases HDL cholesterol, lowers triglyceride levels, diminishes insulin resistance, and reduces the prevalence of metabolic syndrome. Almost half of the metabolic effects, including adiponectin increase, occur beyond weight loss, suggesting a direct peripheral effect of rimonabant.

Published
2006

49. Effects of sibutramine on ventricular dimensions and heart valves in obese patients during weight reduction.

Author

Zannad F, Gille B, Grentzinger A, Bruntz JF, Hammadi M, Boivin JM, Hanotin C, Igau B, and Drouin P

Subjects
Adolescent, Adult, Aged, Blood Pressure drug effects, Body Mass Index, Double-Blind Method, Echocardiography drug effects, Electrocardiography drug effects, Female, Heart Rate drug effects, Heart Valves anatomy & histology, Heart Ventricles anatomy & histology, Humans, Male, Middle Aged, Placebos, Pulse statistics & numerical data, Weight Loss drug effects, Appetite Depressants pharmacology, Appetite Depressants therapeutic use, Cyclobutanes pharmacology, Cyclobutanes therapeutic use, Heart Valves drug effects, Heart Ventricles drug effects, Obesity drug therapy
Abstract

Background: Obesity enhances hemodynamic alterations that predispose to a subsequent increase in left ventricular (LV) wall stress leading to LV hypertrophy. In obese subjects, weight reduction regresses LV mass (LVM), regardless of blood pressure. Sibutramine can increase blood pressure and heart rate, which may attenuate the reductions in LVM associated with weight loss., Methods: Outpatients (n = 184, age 18-65 y, body mass index > or =30 to <40 kg/m2) were randomly assigned to 6 months of once daily double-blind treatment with sibutramine 10 mg or 20 mg, or placebo. LV dimensions, status and function of the valves, weight loss, blood pressure, heart rate, and electrocardiogram were assessed., Results: For end point data sets, the mean +/- SD LVM index (LVM/height) changes were -3.0 +/- 11.9 g/m for placebo (n = 56), -4.4 +/- 10.7 g/m for sibutramine 10 mg (n = 61), and -4.3 +/- 10.9 g/m for sibutramine 20 mg (n = 56). The reductions observed in the sibutramine groups were statistically significant compared with baseline (P <.01), but pairwise comparison results with placebo were not statistically significant. There was no difference in overall status of the cardiac valves. A statistically significant greater weight loss was found in patients on both doses of sibutramine compared with placebo (P <.001). No statistically significant differences between the groups were observed in respect to blood pressure and electrocardiographic intervals, but a statistically significant increase in pulse rate (7 beats/min) was noted for patients with sibutramine treatment., Conclusion: A 6-month treatment with sibutramine does not affect ventricular dimensions, heart valves, and electrocardiogram variables.

Published
2002
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50. A comparison of sibutramine and dexfenfluramine in the treatment of obesity.

Author

Hanotin C, Thomas F, Jones SP, Leutenegger E, and Drouin P

Subjects
Adult, Appetite Depressants administration & dosage, Appetite Depressants adverse effects, Body Constitution, Body Mass Index, Cyclobutanes administration & dosage, Cyclobutanes adverse effects, Dexfenfluramine administration & dosage, Dexfenfluramine adverse effects, Double-Blind Method, Drug Administration Schedule, Female, Humans, Male, Middle Aged, Serotonin Receptor Agonists administration & dosage, Serotonin Receptor Agonists adverse effects, Treatment Outcome, Appetite Depressants therapeutic use, Body Weight drug effects, Cyclobutanes therapeutic use, Dexfenfluramine therapeutic use, Obesity drug therapy, Serotonin Receptor Agonists therapeutic use
Abstract

Objective: Because long-term weight reduction is often unsuccessful with dietary restriction alone, pharmacological agents have been used to promote weight loss. We have compared the novel (multiple monoamine neurotransmitter reuptake inhibitor) antiobesity drug sibutramine (10 mg once daily) with the extensively studied serotonin-releasing antiobesity agent dexfenfluramine (15 mg twice daily)., Research Methods and Procedures: 226 healthy outpatients (aged 18 to 65 years; body mass index > or =27 kg/m2) were included in a 12-week, randomized, double-blind, parallel group study. The main outcome measures were changes in weight, body mass index, waist and hip circumference and ratio, and safety profiles., Results: Mean (+/-SEM) absolute weight loss was 4.5 +/- 0.4 kg in the sibutramine group (n = 112) and 3.2 +/- 0.3 kg in the dexfenfluramine group (n = 112) (endpoint analysis); 4.7 +/- 0.4 kg in the sibutramine group (n = 101); and 3.6 +/- 0.3 kg in the dexfenfluramine group (n = 94) (completers analysis). Comparing the two treatments under the conventional null hypothesis of equality as a secondary analysis, weight loss at endpoint in patients receiving sibutramine was significantly greater than that achieved with dexfenfluramine (p<0.05). Both drugs had similar adverse events profiles: 174 patients (77%) experienced adverse events; 17 patients withdrew due to adverse events (sibutramine, n = 6; dexfenfluramine, n = 11). Pulse rate increased significantly in sibutramine-treated patients (3.6 bpm), but decreased in dexfenfluramine-treated patients (-0.9 bpm)., Discussion: Sibutramine (10 mg once daily) is at least as effective as dexfenfluramine (15 mg twice daily) in achieving weight loss in patients with obesity.

Published
1998
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