88 results on '"Kralova K"'
Search Results
2. S285: INHIBITION OF COMPLEMENT C1S WITH SUTIMLIMAB IN PATIENTS WITH COLD AGGLUTININ DISEASE (CAD): 2-YEAR FOLLOW-UP FROM THE CARDINAL STUDY
- Author
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Röth, A., primary, Barcellini, W., additional, D’Sa, S., additional, Miyakawa, Y., additional, Broome, C. M., additional, Michel, M., additional, Kuter, D. J., additional, Jilma, B., additional, Tvedt, T. H. A., additional, Weitz, I. C., additional, Sourdille, T., additional, Wang, J., additional, Vagge, D. S., additional, Kralova, K., additional, Shafer, F., additional, Wardecki, M., additional, Lee, M., additional, and Berentsen, S., additional
- Published
- 2022
- Full Text
- View/download PDF
3. P1538: INHIBITION OF COMPLEMENT C1S WITH SUTIMLIMAB IN PATIENTS WITH COLD AGGLUTININ DISEASE (CAD): RESULTS FOLLOWING 9-WEEK WASHOUT PERIOD IN PHASE 3 CARDINAL STUDY (NCT03347396)
- Author
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Röth, A., primary, Barcellini, W., additional, D’Sa, S., additional, Miyakawa, Y., additional, Broome, C. M., additional, Michel, M., additional, Kuter, D. J., additional, Jilma, B., additional, Tvedt, T. H. A., additional, Weitz, I. C., additional, Sourdille, T., additional, Wang, J., additional, Vagge, D. S., additional, Kralova, K., additional, Shafer, F., additional, Wardecki, M., additional, Lee, M., additional, and Berentsen, S., additional
- Published
- 2022
- Full Text
- View/download PDF
4. 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
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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, 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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, 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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., Park H. T., 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. T., Massey C., Wattanakit K., O'Donnell P. J., 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. J., Claxton E., Weiss R., Kathryn R., Berk M., Rossi P., Joshi P., Khera A., Khaira A. 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F., 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., 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., Butters J., Griffith L., Shaw M., Grunberg L., Islam S., Bregeault M. -F., 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. A., and McClanahan M. A.
- 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 HbA1c 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
- Published
- 2019
5. Effect of Alirocumab on Mortality After Acute Coronary Syndromes An Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial
- Author
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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.
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- 2019
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6. Alirocumab Reduces Total Hospitalizations and Increases Days Alive and Out of Hospital in the ODYSSEY OUTCOMES Trial
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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, 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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, 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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
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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.
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- 2019
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7. Thromboembolic (TE) Events in Cold Agglutinin Disease (CAD): Post-hoc Analysis PRE- and ON-sutimlimab Treatment in the Phase 3 CARDINAL and CADENZA Studies.
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Röth, A., Ueda, Y., McCrae, K., Khan, U., Kralova, K., Wardȩcki, M., Shafer, F., Yoo, R., and Broome, C.
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- 2024
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8. Open-label ODYSSEY APPRISE study: Interim data from the first 843 participants
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Henry, P., primary, Cariou, B., additional, Averna, M., additional, Gaudet, D., additional, Lopez-Sendon, J.L., additional, Drouot, D., additional, Chibedi-De-Roche, D., additional, Samuel, R., additional, Saubadu, S., additional, Kralova, K., additional, Huber, K., additional, Mertens, A., additional, and Ceska, R., additional
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- 2018
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9. Interactions of β-Cyclodextrin with Ionic Detergents
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Kraľova, K., Mitterhauszerová, Ľ., and Szejtli, J., editor
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- 1982
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10. P1502Open-label ODYSSEY APPRISE study: interim data from the first 843 participants
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Cariou, B., primary, Averna, M., additional, Henry, P., additional, Gaudet, D., additional, Lopez-Sendon, J.L., additional, Drouot, D., additional, Chibedi-De-Roche, D., additional, Samuel, R., additional, Saubadu, S., additional, Kralova, K., additional, Huber, K., additional, Mertens, A., additional, and Ceska, R., additional
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- 2017
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11. ChemInform Abstract: 3-Substituted 6-Bromo-2-benzothiazolinones and Their Antialgal and Plant Growth Regulating Activity.
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SIDOOVA, E., primary, GVOZDJAKOVA, A., additional, KRALOVA, K., additional, and MITTERHAUSZEROVA, L., additional
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- 2010
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12. ChemInform Abstract: Inhibition of Photosynthetic Electron Transport by Some Anilides of 2-Alkylpyridine-4-carboxylic Acids in Spinach Chloroplasts.
- Author
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KRALOVA, K., primary, SERSEN, F., additional, MILETIN, M., additional, and HARTL, J., additional
- Published
- 2010
- Full Text
- View/download PDF
13. ChemInform Abstract: Inhibition of Oxygen Evolution Rate in Freshwater Algae Chlorella vulgaris by Some Anilides of Substituted Pyridine-4-carboxylic Acids
- Author
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Kralova, K., primary, Miletin, M., additional, and Dolezal, M., additional
- Published
- 2010
- Full Text
- View/download PDF
14. Quinaldine Derivatives: Preparation and Biological Activity
- Author
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Jampilek, J., primary, Dolezal, M., additional, Kunes, J., additional, Buchta, V., additional, Silva, L., additional, and Kralova, K., additional
- Published
- 2005
- Full Text
- View/download PDF
15. Synthesis and Biological Activity of 2-Amino-N-phenylbenzamides and 3-Phenyl-1,2,3-benzotriazin-4(3H)-ones
- Author
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Kubicova, L., primary, Dostal, H., additional, Kunes, J., additional, Kralova, K., additional, Buchta, V., additional, Kaustova, J., additional, and Waisser, K., additional
- Published
- 2000
- Full Text
- View/download PDF
16. Synthesis of Some 2, 6-Disubstituted 4-Amidopyridines and -Thioamidopyridines, and Their Antimycobacterial and Photosynthesis-Inhibiting Activity
- Author
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Miletin, Miroslav, primary, Hartl, Jiri, additional, Dolezal, Martin, additional, Odlerova, Z., additional, Kralova, K., additional, and Machacek, Milos, additional
- Published
- 2000
- Full Text
- View/download PDF
17. ChemInform Abstract: Synthesis and Photosynthesis‐Inhibiting Activity of Some Anilides of Substituted Pyrazine‐2‐carboxylic Acids.
- Author
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Dolezal, M., primary, Hartl, J., additional, Miletin, M., additional, Machacek, M., additional, and Kralova, K., additional
- Published
- 1999
- Full Text
- View/download PDF
18. Synthesis of N,N'-diarylalkanediamides and their antimycobacterial and antialgal activity
- Author
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Kubicova, L., primary, Waisser, K., additional, Kunes, J., additional, Kralova, K., additional, Odlerova, Z., additional, Slosarek, M., additional, Janota, J., additional, and Svoboda, Z., additional
- Published
- 1999
- Full Text
- View/download PDF
19. Long Chain Bisquaternary Ammonium Salts - Effective Inhibitors of Photosynthesis
- Author
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Kralova, K., primary and Sersen, F., additional
- Published
- 1994
- Full Text
- View/download PDF
20. ChemInform Abstract: 3‐Alkyl Derivatives of 6‐Acetamido‐ and 6‐Nitro‐2‐benzothiazolinones as Plant Growth Stimulators.
- Author
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SIDOOVA, E., primary, KRALOVA, K., additional, and MITTERHAUSZEROVA, L., additional
- Published
- 1993
- Full Text
- View/download PDF
21. Synthesis of 2-benzylthiopyridine-4-carbothioamide derivatives and their antimycobacterial, antifungal and photosynthesis- inhibiting activity
- Author
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Klimesova, V., Svoboda, M., Waisser, K., Kaustova, J., Buchta, V., and Kralova, K.
- Published
- 1999
- Full Text
- View/download PDF
22. Studium der Mizellbildungsprozesse von Tensiden des Typs N,N’-bis(Alkyldimethyl)-1,6-hexandiammoniumdibromid in wäßrigen Lösungen
- Author
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Kralova, K., primary and Mitterhauszeroväa, L., additional
- Published
- 1983
- Full Text
- View/download PDF
23. Interactions of B-Cyclodextrin with Surface Active Compounds
- Author
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Mitterhauszerova, I., primary and Kralova, K., additional
- Published
- 1989
- Full Text
- View/download PDF
24. ChemInform Abstract: Inhibition of Oxygen Evolution Rate in Freshwater Algae Chlorella vulgaris by Some Anilides of Substituted Pyridine-4-carboxylic Acids.
- Author
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Kralova, K., Miletin, M., and Dolezal, M.
- Published
- 2002
- Full Text
- View/download PDF
25. ChemInform Abstract: 3-Substituted 6-Bromo-2-benzothiazolinones and Their Antialgal and Plant Growth Regulating Activity.
- Author
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SIDOOVA, E., GVOZDJAKOVA, A., KRALOVA, K., and MITTERHAUSZEROVA, L.
- Published
- 1993
- Full Text
- View/download PDF
26. ChemInform Abstract: Inhibition of Photosynthetic Electron Transport by Some Anilides of 2-Alkylpyridine-4-carboxylic Acids in Spinach Chloroplasts.
- Author
-
KRALOVA, K., SERSEN, F., MILETIN, M., and HARTL, J.
- Published
- 1998
- Full Text
- View/download PDF
27. 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
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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 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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, 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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.
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- 2019
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28. Comprehensive spectroscopic, metabolomic, and proteomic liquid biopsy in the diagnostics of hepatocellular carcinoma.
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Kralova K, Vrtelka O, Fouskova M, Smirnova TA, Michalkova L, Hribek P, Urbanek P, Kuckova S, and Setnicka V
- Subjects
- Humans, Proteomics methods, Liver Cirrhosis diagnosis, Spectrum Analysis, Liquid Biopsy, Carcinoma, Hepatocellular, Liver Neoplasms diagnosis
- Abstract
Liquid biopsy is a very topical issue in clinical diagnostics research nowadays. In this study, we explored and compared various analytical approaches to blood plasma analysis. Finally, we proposed a comprehensive procedure, which, thanks to the utilization of multiple analytical techniques, allowed the targeting of various biomolecules in blood plasma reflecting diverse biological processes underlying disease development. The potential of such an approach, combining proteomics, metabolomics, and vibrational spectroscopy along with preceding blood plasma fractionation, was demonstrated on blood plasma samples of patients suffering from hepatocellular carcinoma in cirrhotic terrain (n = 20) and control subjects with liver cirrhosis (n = 20) as well as healthy subjects (n = 20). Most of the applied methods allowed the classification of the samples with an accuracy exceeding 80.0 % and therefore have the potential to be used as a stand-alone method in clinical diagnostics. Moreover, a final panel of 48 variables obtained by a combination of the utilized analytical methods enabled the discrimination of the hepatocellular carcinoma samples from cirrhosis with 94.3 % cross-validated accuracy. Thus, this study, although limited by the cohort size, clearly demonstrated the benefit of the multimethod approach in clinical diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
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- 2024
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29. Raman spectroscopy and Raman optical activity of blood plasma for differential diagnosis of gastrointestinal cancers.
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Kralova K, Vrtelka O, Fouskova M, Hribek P, Bunganic B, Miskovicova M, Urbanek P, Zavoral M, Petruzelka L, Habartova L, and Setnicka V
- Subjects
- Humans, Spectrum Analysis, Raman methods, Diagnosis, Differential, Optical Rotation, Plasma chemistry, Discriminant Analysis, Principal Component Analysis, Gastrointestinal Neoplasms, Colorectal Neoplasms
- Abstract
Improving the early diagnosis of gastrointestinal cancers is a crucial step in reducing their mortality. Given the non-specificity of the initial symptoms, the ability of any diagnostic method to differentiate between various types of gastrointestinal cancers also needs to be addressed. To detect disease-specific alterations in biomolecular structure and composition of the blood plasma, we have implemented an approach combining Raman spectroscopy and its conformation-sensitive polarized version, Raman optical activity, to analyze blood plasma samples of patients suffering from three different types of gastrointestinal cancer - hepatocellular, colorectal and pancreatic. First, we aimed to discriminate any type of gastrointestinal cancer from healthy control individuals; inthenext step, the focus was on differentiating among the three cancer types studied. The more straightforward of the two statistical approaches tested, the combination of linear discriminant analysis and principal component analysis applied to the entire spectral dataset, allowed the discrimination of cancer and control samples with 87% accuracy. The three gastrointestinal cancers were classified with an overall accuracy of 76%. The second method, the linear discriminant analysis applied to a selection of spectral bands, yielded even higher values. Cancer and control samples were distinguished with 89% accuracy and hepatocellular, colorectal and pancreatic cancer with an overall accuracy of 87%. The results obtained in our study suggest that the proposed approach may become a disease-specific diagnostic tool in daily clinical practice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
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- 2024
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30. Comparative study of Raman spectroscopy techniques in blood plasma-based clinical diagnostics: A demonstration on Alzheimer's disease.
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Kralova K, Kral M, Vrtelka O, and Setnicka V
- Abstract
Nowadays, there are still many diseases with limited or no reliable methods of early diagnosis. A popular approach in clinical diagnostic research is Raman spectroscopy, as a relatively simple, cost-effective, and high-throughput method for searching for disease-specific alterations in the composition of blood plasma. However, the high variability of the experimental designs, targeted diseases, or statistical processing in the individual studies makes it challenging to compare and compile the results to critically assess the applicability of Raman spectroscopy in real clinical practice. This study aimed to compare data from a single series of blood plasma samples of patients with Alzheimer's disease and non-demented elderly controls obtained by four different techniques/experimental setups - Raman spectroscopy with excitation at 532 and 785 nm, Raman optical activity, and surface-enhanced Raman scattering spectroscopy. The obtained results showed that the spectra from each Raman spectroscopy technique contain different information about biomolecules of blood plasma or their conformation and may, therefore, offer diverse points of view on underlying biochemical processes of the disease. The classification models based on the datasets generated by the three non-chiroptical variants of Raman spectroscopy exhibited comparable diagnostic performance, all reaching an accuracy close to or equal to 80%. Raman optical activity achieved only 60% classification accuracy, suggesting its limited applicability in the specific case of Alzheimer's disease diagnostics. The described differences in the outputs of the four utilized techniques/setups of Raman spectroscopy imply that their choice may crucially affect the acquired results and thus should be approached carefully concerning the specific purpose., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
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- 2024
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31. Sustained inhibition of complement C1s with sutimlimab over 2 years in patients with cold agglutinin disease.
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Röth A, Barcellini W, D'Sa S, Miyakawa Y, Broome CM, Michel M, Kuter DJ, Jilma B, Tvedt THA, Weitz IC, Yoo R, Jayawardene D, Vagge DS, Kralova K, Shafer F, Wardȩcki M, Lee M, and Berentsen S
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- Humans, Complement C1s, Hemolysis, Quality of Life, Clinical Trials, Phase III as Topic, Anemia, Hemolytic, Autoimmune drug therapy
- Abstract
Cold agglutinin disease (CAD) is a rare, autoimmune, classical complement pathway (CP)-mediated hemolytic anemia. Sutimlimab selectively inhibits C1s of the C1 complex, preventing CP activation while leaving the alternative and lectin pathways intact. In Part A (26 weeks) of the open-label, single-arm, Phase 3 CARDINAL study in patients with CAD and a recent history of transfusion, sutimlimab demonstrated rapid effects on hemolysis and anemia. Results of the CARDINAL study Part B (2-year extension) study, described herein, demonstrated that sutimlimab sustains improvements in hemolysis, anemia, and quality of life over a median of 144 weeks of treatment. Mean last-available on-treatment values in Part B were improved from baseline for hemoglobin (12.2 g/dL on-treatment versus 8.6 g/dL at baseline), bilirubin (16.5 μmol/L on-treatment versus 52.1 μmol/L at baseline), and FACIT-Fatigue scores (40.5 on-treatment versus 32.4 at baseline). In the 9-week follow-up period after sutimlimab cessation, CP inhibition was reversed, and hemolytic markers and fatigue scores approached pre-sutimlimab values. Overall, sutimlimab was generally well tolerated in Part B. All 22 patients experienced ≥1 treatment-emergent adverse event (TEAE); 12 (54.5%) patients experienced ≥1 serious TEAE, including seven (31.8%) with ≥1 serious infection. Three patients discontinued due to a TEAE. No patients developed systemic lupus erythematosus or meningococcal infections. After cessation of sutimlimab, most patients reported adverse events consistent with recurrence of CAD. In conclusion, the CARDINAL 2-year results provide evidence of sustained sutimlimab effects for CAD management, but that disease activity reoccurs after treatment cessation. NCT03347396. Registered November 20, 2017., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)
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- 2023
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32. Quality of MedDRA ® Coding in a Sample of COVID-19 Vaccine Medication Error Data.
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Kralova K, Wilson CA, Richebourg N, and D'souza J
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- Humans, Adverse Drug Reaction Reporting Systems, Medication Errors prevention & control, Databases, Factual, COVID-19 Vaccines adverse effects, COVID-19 prevention & control
- Abstract
Introduction: In recent years, there has been increasing interest from regulatory agencies and scientific organisations into the recording, coding and reporting of medication errors. Accuracy and consistency in the handling of medication error reports ensure the safety and effectiveness of medicines and provide reliable information to both healthcare professionals and patients., Objective: The authors have examined a sample of Medical Dictionary for Regulatory Activities (MedDRA
® ) coded reports that describe medication errors to assess the accuracy and consistency of MedDRA® coding, and to identify the main types of coding errors for the newly introduced COVID-19 vaccines., Methods: The sample of coded terms was assessed by two MedDRA® experts applying the Four Eyes Principle. It included 1500 reported terms drawn from the Uppsala Monitoring Centre database reported up to 25 August, 2021, describing medication errors for COVID-19 vaccines with their assigned MedDRA® terms., Results: One third of the records could not be assessed because of incomplete or unclear verbatims. In one third, MedDRA® term assignments were correct, but another third of the sample was not adequately coded. The most frequent coding errors corresponded to vague MedDRA® Preferred Term assignments despite more detailed information being available in the verbatim for a more precise coding. This observation is similar to findings in the EudraVigilance database, where some of the most frequently assigned MedDRA® terms for medication errors also represent vague concepts., Conclusions: The findings indicate that understanding of medication error documentation and of the importance of accurate extraction of information from case narratives, as well as knowledge of MedDRA® content and coding guidelines need to be reinforced. The authors provide useful references to training opportunities and to the applicable International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use-Endorsed Guides for MedDRA® users., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)- Published
- 2023
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33. Insights into Lipid-Based Delivery Nanosystems of Protein-Tyrosine Kinase Inhibitors for Cancer Therapy.
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Jampilek J and Kralova K
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According to the WHO, cancer caused almost 10 million deaths worldwide in 2020, i.e., almost one in six deaths. Among the most common are breast, lung, colon and rectal and prostate cancers. Although the diagnosis is more perfect and spectrum of available drugs is large, there is a clear trend of an increase in cancer that ends fatally. A major advance in treatment was the introduction of gentler antineoplastics for targeted therapy-tyrosine kinase inhibitors (TKIs). Although they have undoubtedly revolutionized oncology and hematology, they have significant side effects and limited efficacy. In addition to the design of new TKIs with improved pharmacokinetic and safety profiles, and being more resistant to the development of drug resistance, high expectations are placed on the reformulation of TKIs into various drug delivery lipid-based nanosystems. This review provides an insight into the history of chemotherapy, a brief overview of the development of TKIs for the treatment of cancer and their mechanism of action and summarizes the results of the applications of self-nanoemulsifying drug delivery systems, nanoemulsions, liposomes, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles and nanostructured lipid carriers used as drug delivery systems of TKIs obtained in vitro and in vivo.
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- 2022
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34. Anticancer Applications of Essential Oils Formulated into Lipid-Based Delivery Nanosystems.
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Jampilek J and Kralova K
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The use of natural compounds is becoming increasingly popular among patients, and there is a renewed interest among scientists in nature-based bioactive agents. Traditionally, herbal drugs can be taken directly in the form of teas/decoctions/infusions or as standardized extracts. However, the disadvantages of natural compounds, especially essential oils, are their instability, limited bioavailability, volatility, and often irritant/allergenic potential. However, these active substances can be stabilized by encapsulation and administered in the form of nanoparticles. This brief overview summarizes the latest results of the application of nanoemulsions, liposomes, solid lipid nanoparticles, and nanostructured lipid carriers used as drug delivery systems of herbal essential oils or used directly for their individual secondary metabolites applicable in cancer therapy. Although the discussed bioactive agents are not typical compounds used as anticancer agents, after inclusion into the aforesaid formulations improving their stability and bioavailability and/or therapeutic profile, they indicated anti-tumor activity and became interesting agents with cancer treatment potential. In addition, co-encapsulation of essential oils with synthetic anticancer drugs into nanoformulations with the aim to achieve synergistic effect in chemotherapy is discussed.
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- 2022
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35. Advances in Biologically Applicable Graphene-Based 2D Nanomaterials.
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Jampilek J and Kralova K
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- Carbon, Humans, Nanotechnology, Graphite, Nanostructures, Quantum Dots therapeutic use
- Abstract
Climate change and increasing contamination of the environment, due to anthropogenic activities, are accompanied with a growing negative impact on human life. Nowadays, humanity is threatened by the increasing incidence of difficult-to-treat cancer and various infectious diseases caused by resistant pathogens, but, on the other hand, ensuring sufficient safe food for balanced human nutrition is threatened by a growing infestation of agriculturally important plants, by various pathogens or by the deteriorating condition of agricultural land. One way to deal with all these undesirable facts is to try to develop technologies and sophisticated materials that could help overcome these negative effects/gloomy prospects. One possibility is to try to use nanotechnology and, within this broad field, to focus also on the study of two-dimensional carbon-based nanomaterials, which have excellent prospects to be used in various economic sectors. In this brief up-to-date overview, attention is paid to recent applications of graphene-based nanomaterials, i.e., graphene, graphene quantum dots, graphene oxide, graphene oxide quantum dots, and reduced graphene oxide. These materials and their various modifications and combinations with other compounds are discussed, regarding their biomedical and agro-ecological applications, i.e., as materials investigated for their antineoplastic and anti-invasive effects, for their effects against various plant pathogens, and as carriers of bioactive agents (drugs, pesticides, fertilizers) as well as materials suitable to be used in theranostics. The negative effects of graphene-based nanomaterials on living organisms, including their mode of action, are analyzed as well.
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- 2022
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36. Advances in Nanostructures for Antimicrobial Therapy.
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Jampilek J and Kralova K
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Microbial infections caused by a variety of drug-resistant microorganisms are more common, but there are fewer and fewer approved new antimicrobial chemotherapeutics for systemic administration capable of acting against these resistant infectious pathogens. Formulation innovations of existing drugs are gaining prominence, while the application of nanotechnologies is a useful alternative for improving/increasing the effect of existing antimicrobial drugs. Nanomaterials represent one of the possible strategies to address this unfortunate situation. This review aims to summarize the most current results of nanoformulations of antibiotics and antibacterial active nanomaterials. Nanoformulations of antimicrobial peptides, synergistic combinations of antimicrobial-active agents with nitric oxide donors or combinations of small organic molecules or polymers with metals, metal oxides or metalloids are discussed as well. The mechanisms of actions of selected nanoformulations, including systems with magnetic, photothermal or photodynamic effects, are briefly described.
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- 2022
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37. Advances in Drug Delivery Nanosystems Using Graphene-Based Materials and Carbon Nanotubes.
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Jampilek J and Kralova K
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Carbon is one of the most abundant elements on Earth. In addition to the well-known crystallographic modifications such as graphite and diamond, other allotropic carbon modifications such as graphene-based nanomaterials and carbon nanotubes have recently come to the fore. These carbon nanomaterials can be designed to help deliver or target drugs more efficiently and to innovate therapeutic approaches, especially for cancer treatment, but also for the development of new diagnostic agents for malignancies and are expected to help combine molecular imaging for diagnosis with therapies. This paper summarizes the latest designed drug delivery nanosystems based on graphene, graphene quantum dots, graphene oxide, reduced graphene oxide and carbon nanotubes, mainly for anticancer therapy.
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- 2021
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38. Potential of Nanonutraceuticals in Increasing Immunity.
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Jampilek J and Kralova K
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Nutraceuticals are defined as foods or their extracts that have a demonstrably positive effect on human health. According to the decision of the European Food Safety Authority, this positive effect, the so-called health claim, must be clearly demonstrated best by performed tests. Nutraceuticals include dietary supplements and functional foods. These special foods thus affect human health and can positively affect the immune system and strengthen it even in these turbulent times, when the human population is exposed to the COVID-19 pandemic. Many of these special foods are supplemented with nanoparticles of active substances or processed into nanoformulations. The benefits of nanoparticles in this case include enhanced bioavailability, controlled release, and increased stability. Lipid-based delivery systems and the encapsulation of nutraceuticals are mainly used for the enrichment of food products with these health-promoting compounds. This contribution summarizes the current state of the research and development of effective nanonutraceuticals influencing the body's immune responses, such as vitamins (C, D, E, B
12 , folic acid), minerals (Zn, Fe, Se), antioxidants (carotenoids, coenzyme Q10, polyphenols, curcumin), omega-3 fatty acids, and probiotics.- Published
- 2020
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39. Potential of Nanomaterial Applications in Dietary Supplements and Foods for Special Medical Purposes.
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Jampilek J, Kos J, and Kralova K
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Dietary supplements and foods for special medical purposes are special medical products classified according to the legal basis. They are regulated, for example, by the European Food Safety Authority and the U.S. Food and Drug Administration, as well as by various national regulations issued most frequently by the Ministry of Health and/or the Ministry of Agriculture of particular countries around the world. They constitute a concentrated source of vitamins, minerals, polyunsaturated fatty acids and antioxidants or other compounds with a nutritional or physiological effect contained in the food/feed, alone or in combination, intended for direct consumption in small measured amounts. As nanotechnology provides "a new dimension" accompanied with new or modified properties conferred to many current materials, it is widely used for the production of a new generation of drug formulations, and it is also used in the food industry and even in various types of nutritional supplements. These nanoformulations of supplements are being prepared especially with the purpose to improve bioavailability, protect active ingredients against degradation, or reduce side effects. This contribution comprehensively summarizes the current state of the research focused on nanoformulated human and veterinary dietary supplements, nutraceuticals, and functional foods for special medical purposes, their particular applications in various food products and drinks as well as the most important related guidelines, regulations and directives.
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- 2019
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40. Halogenated 1-Hydroxynaphthalene-2-Carboxanilides Affecting Photosynthetic Electron Transport in Photosystem II.
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Gonec T, Kos J, Pesko M, Dohanosova J, Oravec M, Liptaj T, Kralova K, and Jampilek J
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- Chloroplasts drug effects, Chloroplasts metabolism, Inhibitory Concentration 50, Spinacia oleracea drug effects, Spinacia oleracea metabolism, Electron Transport drug effects, Naphthols chemical synthesis, Naphthols chemistry, Naphthols pharmacology, Photosynthesis drug effects, Photosystem II Protein Complex metabolism
- Abstract
Series of seventeen new multihalogenated 1-hydroxynaphthalene-2-carboxanilides was prepared and characterized. All the compounds were tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach ( Spinacia oleracea L.) chloroplasts. 1-Hydroxy- N -phenylnaphthalene-2-carboxamides substituted in the anilide part by 3,5-dichloro-, 4-bromo-3-chloro-, 2,5-dibromo- and 3,4,5-trichloro atoms were the most potent PET inhibitors (IC
50 = 5.2, 6.7, 7.6 and 8.0 µM, respectively). The inhibitory activity of these compounds depends on the position and the type of halogen substituents, i.e., on lipophilicity and electronic properties of individual substituents of the anilide part of the molecule. Interactions of the studied compounds with chlorophyll a and aromatic amino acids present in pigment-protein complexes mainly in PS II were documented by fluorescence spectroscopy. The section between P680 and plastoquinone QB in the PET chain occurring on the acceptor side of PS II can be suggested as the site of action of the compounds. The structure-activity relationships are discussed., Competing Interests: The authors declare no conflicts of interest.- Published
- 2017
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41. Photosynthesis-Inhibiting Activity of 1-[(2-Chlorophenyl)carbamoyl]- and 1-[(2-Nitrophenyl)carbamoyl]naphthalen-2-yl Alkylcarbamates.
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Gonec T, Stranik J, Pesko M, Kos J, Oravec M, Kralova K, and Jampilek J
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- Carbamates chemistry, Chloroplasts drug effects, Chloroplasts metabolism, Inhibitory Concentration 50, Spinacia oleracea metabolism, Structure-Activity Relationship, Carbamates pharmacology, Electron Transport drug effects, Photosynthesis drug effects
- Abstract
Eight 1-[(2-chlorophenyl)carbamoyl]naphthalen-2-yl alkylcarbamates and eight 1-[(2-nitrophenyl)carbamoyl]naphthalen-2-yl alkylcarbamates were tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach ( Spinacia oleracea L.) chloroplasts. The PET-inhibiting activity of the compounds was relatively low; the corresponding IC
50 values ranged from 0.05 to 0.664 mmol/L; and the highest activity within the series of compounds was observed for 1-[(2-chlorophenyl)-carbamoyl]naphthalen-2-yl propylcarbamate. It has been proven that the compounds are PET-inhibitors in photosystem II. Despite rather low PET-inhibiting activities, primary structure-activity trends can be discussed., Competing Interests: The authors declare no conflict of interest.- Published
- 2017
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42. Antimycobacterial N-alkoxyphenylhydroxynaphthalenecarboxamides affecting photosystem II.
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Gonec T, Kralova K, Pesko M, and Jampilek J
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- Anti-Bacterial Agents chemistry, Electron Transport drug effects, Naphthalenes chemistry, Photosystem II Protein Complex metabolism, Plant Proteins metabolism, Spinacia oleracea metabolism, Anti-Bacterial Agents metabolism, Naphthalenes metabolism, Photosystem II Protein Complex antagonists & inhibitors, Plant Proteins antagonists & inhibitors, Spinacia oleracea drug effects
- Abstract
N-(Alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides (series A) and N-(alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides (series B) affecting photosystem (PS) II inhibited photosynthetic electron transport (PET) in spinach chloroplasts. Their inhibitory activity depended on the compound lipophilicity as well as on the position of the alkoxy substituent. The most potent PET inhibitors were 2-hydroxy-N-phenylnaphthalene-1-carboxamide and N-[3-(but-2-yloxy)phenyl]-2-hydroxynaphthalene-1-carboxamide within series A (IC
50 =28.9 and 42.5µM, respectively) and 1-hydroxy-N-(3-propoxyphenyl)naphthalene-2-carboxamide and 1-hydroxy-N-(3-ethoxyphenyl)-naphthalene-2-carboxamide (IC50 =2.0 and 3.1µM, respectively) within series B. The inhibitory activity of C'(3) or C'(4) alkoxy substituted compounds of series B was considerably higher than that of C'(2) ones within series A. The PET-inhibiting activities of both series were compared with the PET inhibition of isomeric N-alkoxyphenyl-3-hydroxynaphthalene-2-carboxamides (series C) reported recently. Interactions of the studied compounds with chlorophyll a and aromatic amino acids present in pigment-protein complexes mainly in PS II were documented by fluorescence spectroscopy. The section between P680 and plastoquinone QB in the PET chain occurring on the acceptor side of PSII can be suggested as the site of action of the compounds., (Copyright © 2017 Elsevier Ltd. All rights reserved.)- Published
- 2017
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43. Ring-substituted 8-hydroxyquinoline-2-carboxanilides as photosystem II inhibitors.
- Author
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Jampilek J, Kralova K, Pesko M, and Kos J
- Subjects
- Anilides chemical synthesis, Anilides metabolism, Chlorophyll chemistry, Chlorophyll A, Chloroplasts metabolism, Electron Transport, Photosynthesis, Photosystem II Protein Complex metabolism, Protein Binding, Spectrometry, Fluorescence, Spinacia oleracea metabolism, Structure-Activity Relationship, Anilides chemistry, Oxyquinoline chemistry, Photosystem II Protein Complex antagonists & inhibitors
- Abstract
Ring-substituted 8-hydroxyquinoline-2-carboxanilides inhibited photosynthetic electron transport (PET) through photosystem (PS) II. Their inhibitory efficiency depended on the compound lipophilicity, the electronic properties of the substituent R and the position of the substituent R on the benzene ring. The most effective inhibitors showing IC50 values in the range 2.3-3.6μM were substituted in C'(3) by F, CH3, Cl and Br. The dependence of the PET-inhibiting activity on the lipophilicity of the compounds was quasi-parabolic for 3-substituted derivatives, while for C'(2) ones a slight increase and for C'(4) derivatives a sharp decrease of the activity were observed with increasing lipophilicity. In addition, the dependence of PET-inhibiting activity on electronic Hammett's σ parameter of the substituent R was observed with optimum σ value 0.06 for C'(4) and 0.34 for C'(3) substituted derivatives, while the value of σ parameter did not significantly influence the PET-inhibiting activity of C'(2) substituted compounds. Interactions of the studied compounds with chlorophyll a and aromatic amino acids present in the pigment-protein complexes mainly in PS II were documented by fluorescence spectroscopy. The section between P680 and plastoquinone QB occurring on the acceptor side of PS II can be suggested as the site of action of the compounds., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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44. Ring-substituted 8-hydroxyquinoline-2-carboxanilides as potential antimycobacterial agents.
- Author
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Kos J, Zadrazilova I, Nevin E, Soral M, Gonec T, Kollar P, Oravec M, Coffey A, O'Mahony J, Liptaj T, Kralova K, and Jampilek J
- Subjects
- Cell Line, Drug Evaluation, Preclinical methods, Humans, Microbial Sensitivity Tests, Mycobacterium avium drug effects, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis metabolism, Oxyquinoline chemistry, Toxicity Tests, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents pharmacology, Structure-Activity Relationship
- Abstract
In this study, a series of twenty-two ring-substituted 8-hydroxyquinoline-2-carboxanilides was prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Mycobacterium tuberculosis H37Ra, Mycobacterium avium complex and M. avium subsp. paratuberculosis. Some of the tested compounds showed the antimycobacterial activity against M. avium subsp. paratuberculosis comparable with or higher than that of rifampicin. 8-Hydroxy-N-[3-(trifluoromethyl)phenyl]- and 8-hydroxy-N-[4-(trifluoromethyl)phenyl]quinoline-2-carboxamide showed MIC=24 μM against all tested mycobacterial strains. 3-Methoxyphenyl- and 3-methylphenyl derivatives expressed MIC=27 or 29 μM also against all the tested strains. Their activity against M. avium subsp. paratuberculosis was 4-fold higher than that of rifampicin. 2-Bromophenyl- and 2-(trifluoromethyl)phenyl derivatives had MIC=23 or 24 μM against M. tuberculosis. A significant decrease of mycobacterial cell metabolism (viability of M. tuberculosis H37Ra) was observed using MTT assay. Screening of cytotoxicity of the compounds was performed using the THP-1 cells, and no significant lethal effect was observed up to tested concentration 30 μM. The structure-activity relationships are discussed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
45. Synthesis and Biological Evaluation of N-Alkoxyphenyl-3-hydroxynaphthalene-2-carboxanilides.
- Author
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Gonec T, Zadrazilova I, Nevin E, Kauerova T, Pesko M, Kos J, Oravec M, Kollar P, Coffey A, O'Mahony J, Cizek A, Kralova K, and Jampilek J
- Subjects
- Ampicillin pharmacology, Anilides chemical synthesis, Anti-Bacterial Agents chemical synthesis, Cell Line, Cell Survival drug effects, Chloroplasts drug effects, Chloroplasts physiology, Electron Transport drug effects, Electron Transport physiology, Humans, Methicillin-Resistant Staphylococcus aureus drug effects, Methicillin-Resistant Staphylococcus aureus growth & development, Microbial Sensitivity Tests, Microbial Viability drug effects, Monocytes cytology, Monocytes drug effects, Mycobacterium avium subsp. paratuberculosis drug effects, Mycobacterium avium subsp. paratuberculosis growth & development, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis growth & development, Naphthalenes chemical synthesis, Photosynthesis drug effects, Photosynthesis physiology, Rifampin pharmacology, Spinacia oleracea drug effects, Spinacia oleracea physiology, Structure-Activity Relationship, Anilides pharmacology, Anti-Bacterial Agents pharmacology, Naphthalenes pharmacology
- Abstract
A series of fifteen new N-alkoxyphenylanilides of 3-hydroxynaphthalene-2-carboxylic acid was prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, three methicillin-resistant S. aureus strains, Mycobacterium tuberculosis H37Ra and M. avium subsp. paratuberculosis. Some of the tested compounds showed antibacterial and antimycobacterial activity against the tested strains comparable with or higher than that of the standards ampicillin or rifampicin. 3-Hydroxy-N-(2-propoxyphenyl)naphthalene-2-carboxamide and N-[2-(but-2-yloxy)-phenyl]-3-hydroxynaphthalene-2-carboxamide had MIC = 12 µM against all methicillin-resistant S. aureus strains; thus their activity is 4-fold higher than that of ampicillin. The second mentioned compound as well as 3-hydroxy-N-[3-(prop-2-yloxy)phenyl]-naphthalene-2-carboxamide had MICs = 23 µM and 24 µM against M. tuberculosis respectively. N-[2-(But-2-yloxy)phenyl]-3-hydroxynaphthalene-2-carboxamide demonstrated higher activity against M. avium subsp. paratuberculosis than rifampicin. Screening of the cytotoxicity of the most effective antimycobacterial compounds was performed using THP-1 cells, and no significant lethal effect was observed for the most potent compounds. The compounds were additionally tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. N-(3-Ethoxyphenyl)-3-hydroxynaphthalene-2-carboxamide (IC50 = 4.5 µM) was the most active PET inhibitor. The structure-activity relationships are discussed.
- Published
- 2015
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46. Synthesis and Biological Evaluation of N-Alkyl-3-(alkylamino)-pyrazine-2-carboxamides.
- Author
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Semelkova L, Konecna K, Paterova P, Kubicek V, Kunes J, Novakova L, Marek J, Naesens L, Pesko M, Kralova K, Dolezal M, and Zitko J
- Subjects
- Antitubercular Agents chemical synthesis, Bacterial Proteins antagonists & inhibitors, Bacterial Proteins metabolism, Fatty Acid Synthases antagonists & inhibitors, Fatty Acid Synthases metabolism, Microbial Sensitivity Tests, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis metabolism, Pyrazinamide chemical synthesis, Pyrazinamide chemistry, Pyrazines chemical synthesis, Spinacia oleracea metabolism, Structure-Activity Relationship, Antitubercular Agents pharmacology, Chloroplasts metabolism, Electron Transport drug effects, Pyrazinamide pharmacology, Pyrazines pharmacology
- Abstract
A series of N-alkyl-3-(alkylamino)pyrazine-2-carboxamides and their N-alkyl-3-chloropyrazine-2-carboxamide precursors were prepared. All compounds were characterized by analytical methods and tested for antimicrobial and antiviral activity. The antimycobacterial MIC values against Mycobacterium tuberculosis H37Rv of the most effective compounds, 3-(hexylamino)-, 3-(heptylamino)- and 3-(octylamino)-N-methyl-pyrazine-2-carboxamides 14‒16, was 25 μg/mL. The compounds inhibited photosystem 2 photosynthetic electron transport (PET) in spinach chloroplasts. This activity was strongly connected with the lipophilicity of the compounds. For effective PET inhibition longer alkyl chains in the 3-(alkylamino) substituent in the N-alkyl-3-(alkylamino)pyrazine-2-carboxamide molecule were more favourable than two shorter alkyl chains.
- Published
- 2015
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47. Synthesis and antimycobacterial properties of ring-substituted 6-hydroxynaphthalene-2-carboxanilides.
- Author
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Kos J, Nevin E, Soral M, Kushkevych I, Gonec T, Bobal P, Kollar P, Coffey A, O'Mahony J, Liptaj T, Kralova K, and Jampilek J
- Subjects
- Anilides chemical synthesis, Anilides chemistry, Anti-Bacterial Agents chemical synthesis, Anti-Bacterial Agents chemistry, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Dose-Response Relationship, Drug, Humans, Microbial Sensitivity Tests, Molecular Structure, Mycobacterium cytology, Naphthols chemical synthesis, Naphthols chemistry, Structure-Activity Relationship, Anilides pharmacology, Anti-Bacterial Agents pharmacology, Mycobacterium drug effects, Naphthols pharmacology
- Abstract
In this study, a series of twenty-two ring-substituted 6-hydroxynaphthalene-2-carboxanilides was prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Mycobacterium tuberculosis H37Ra, Mycobacterium avium complex and M. avium subsp. paratuberculosis. Derivatives substituted by trifluoromethyl, bromo, methyl and methoxy moieties in C'(3) and C'(4) positions of the anilide ring showed 2-fold higher activity against M. tuberculosis than isoniazid and 4.5-fold higher activity against M. avium subsp. paratuberculosis than rifampicin. 6-Hydroxy-N-(2-methylphenyl)naphthalene-2-carboxamide had MIC=29 μM against M. avium complex. A significant decrease of mycobacterial cell metabolism (viability of M. tuberculosis H37Ra) was observed using MTT assay. Screening of the cytotoxicity of the most effective antimycobacterial compounds was performed using the THP-1 cells, and no significant lethal effect was observed. The structure-activity relationships are discussed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2015
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48. Structure-activity relationships of N-benzylsalicylamides for inhibition of photosynthetic electron transport.
- Author
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Kralova K, Perina M, Waisser K, and Jampilek J
- Subjects
- Chloroplasts metabolism, Drug Design, Electron Transport drug effects, Models, Chemical, Molecular Structure, Quantitative Structure-Activity Relationship, Salicylamides chemistry, Salicylamides pharmacology, Spinacia oleracea metabolism, Chloroplasts drug effects, Photosynthesis drug effects, Salicylamides chemical synthesis, Spinacia oleracea drug effects
- Abstract
Inhibition of photosynthetic electron transport (PET) in spinach chloroplasts by sixty-one ring-substituted N-benzylsalicylamides was investigated. The inhibitory potency of the compounds expressed by IC50 value varied from 2.0 to 425.3 μmol/L. Several evaluated compounds can be considered as effective PET inhibitors; these include N-(3,4- dichlorobenzyl)-2-hydroxy-5-nitrobenzamide (IC50 = 2.0 μmol/L), 3,5-dibromo-N-(3,4-dichlorobenzyl)-2-hydroxybenzamide (IC50 = 2.3 μmol/L) and 3,5-dibromo-N-(4-chlorobenzyl)-2-hydroxybenzamide (IC50 = 2.6 μmol/L) with activity comparable with that of the standard Diuron (IC50 = 1.9 μmol/L). The PET inhibiting activity increased approximately linearly with increasing lipophilicity of the compounds as well as with the increasing sum of Hammett σ constants of the substituents on the acyl fragment (R(1) = H, 5-OCH3, 5-CH3, 5-Cl, 5-Br, 5-NO2, 4-OCH3, 4-Cl, 3,5-Cl and 3,5-Br) and the benzylamide fragment (R(2) = H, 4-OCH3, 4-CH3, 4-F, 4-Cl and 3,4-Cl). Based on the evaluated structure-PET inhibiting activity relationships (QSAR) it was confirmed that the inhibitory activity of the compounds depends on lipophilicity (log P or distributive parameters π; (1) and π(2)of individual substituents) and electronic properties of the substituents on the acyl (σ(1)) and the benzylamide fragments (σ(2)), the contribution of σ(1) being more significant than that of σ(2).
- Published
- 2015
- Full Text
- View/download PDF
49. Preparation and biological properties of ring-substituted naphthalene-1-carboxanilides.
- Author
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Gonec T, Kos J, Nevin E, Govender R, Pesko M, Tengler J, Kushkevych I, Stastna V, Oravec M, Kollar P, O'Mahony J, Kralova K, Coffey A, and Jampilek J
- Subjects
- Anilides chemical synthesis, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents pharmacology, Chloroplasts drug effects, Chloroplasts metabolism, Electron Transport drug effects, Hydrophobic and Hydrophilic Interactions, Microbial Sensitivity Tests, Mycobacterium avium drug effects, Photosynthesis drug effects, Spinacia oleracea drug effects, Spinacia oleracea metabolism, Structure-Activity Relationship, Anilides chemistry, Anilides pharmacology, Naphthalenes chemistry
- Abstract
In this study, a series of twenty-two ring-substituted naphthalene-1-carboxanilides were prepared and characterized. Primary in vitro screening of the synthesized carboxanilides was performed against Mycobacterium avium subsp. paratuberculosis. N-(2-Methoxyphenyl)naphthalene-1-carboxamide, N-(3-methoxy-phenyl)naphthalene-1-carboxamide, N-(3-methylphenyl)naphthalene-1-carboxamide, N-(4-methylphenyl)naphthalene-1-carboxamide and N-(3-fluorophenyl)naphthalene-1-carboxamide showed against M. avium subsp. paratuberculosis two-fold higher activity than rifampicin and three-fold higher activity than ciprofloxacin. The most effective antimycobacterial compounds demonstrated insignificant toxicity against the human monocytic leukemia THP-1 cell line. The testing of biological activity of the compounds was completed with the study of photosynthetic electron transport (PET) inhibition in isolated spinach (Spinacia oleracea L.) chloroplasts. The PET-inhibiting activity expressed by IC50 value of the most active compound N-[4-(trifluoromethyl)phenyl]naphthalene-1-carboxamide was 59 μmol/L. The structure-activity relationships are discussed.
- Published
- 2014
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50. New potentially active pyrazinamide derivatives synthesized under microwave conditions.
- Author
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Jandourek O, Dolezal M, Kunes J, Kubicek V, Paterova P, Pesko M, Buchta V, Kralova K, and Zitko J
- Subjects
- Antifungal Agents pharmacology, Antitubercular Agents chemical synthesis, Antitubercular Agents pharmacology, Candida albicans drug effects, Chloroplasts drug effects, Chloroplasts metabolism, Electron Transport drug effects, Herbicides pharmacology, Hydrophobic and Hydrophilic Interactions, Inhibitory Concentration 50, Microbial Sensitivity Tests, Microwaves, Mycobacterium tuberculosis drug effects, Photosynthesis drug effects, Pyrazinamide pharmacology, Spinacia oleracea drug effects, Spinacia oleracea metabolism, Staphylococcus epidermidis drug effects, Structure-Activity Relationship, Antifungal Agents chemical synthesis, Herbicides chemical synthesis, Pyrazinamide analogs & derivatives, Pyrazinamide chemical synthesis
- Abstract
A series of 18 N-alkyl substituted 3-aminopyrazine-2-carboxamides was prepared in this work according to previously experimentally set and proven conditions using microwave assisted synthesis methodology. This approach for the aminodehalogenation reaction was chosen due to higher yields and shorter reaction times compared to organic reactions with conventional heating. Antimycobacterial, antibacterial, antifungal and photosynthetic electron transport (PET) inhibiting in vitro activities of these compounds were investigated. Experiments for the determination of lipophilicity were also performed. Only a small number of substances with alicyclic side chain showed activity against fungi which was the same or higher than standards and the biological efficacy of the compounds increased with rising lipophilicity. Nine pyrazinamide derivatives also inhibited PET in spinach chloroplasts and the IC50 values of these compounds varied in the range from 14.3 to 1590.0 μmol/L. The inhibitory activity was connected not only with the lipophilicity, but also with the presence of secondary amine fragment bounded to the pyrazine ring. Structure-activity relationships are discussed as well.
- Published
- 2014
- Full Text
- View/download PDF
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