34 results on '"Grzelakowski, P."'
Search Results
2. Some estimations of the {\L}ojasiewicz exponent
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Grzelakowski, Kacper
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Mathematics - Algebraic Geometry ,14P20, 14P10, 32C07 - Abstract
We strengthen some estimations of the local and global {\L}ojasiewicz exponent for polynomial mappings on closed semialgebraic sets obtained by K.Kurdyka, S.Spodzieja and A.Szlachci\'nska.
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- 2021
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3. Type III contractions and quintic threefolds
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Grzelakowski, Kacper
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Mathematics - Algebraic Geometry ,14J30, 14J32 - Abstract
We study type III contractions of Calabi-Yau threefolds containing a ruled surface over a smooth curve. We discuss the conditions necessary for the image threefold to by smoothable. We describe the change in Hodge numbers caused by this contraction and smoothing deformation. A generalization of a fomula for calculating Hodge numbers of hypersurfaces in $\mathbb{P}^4$ with ordinary double and triple points is presented. We use these results to construct new Calabi-Yau threefolds of Picard rank two arising from a family of quintic threefolds containing a cone.
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- 2020
4. Rapid fabrication of precise high-throughput filters from membrane protein nanosheets
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Tu, Yu-Ming, Song, Woochul, Ren, Tingwei, Shen, Yue-xiao, Chowdhury, Ratul, Rajapaksha, Prasangi, Culp, Tyler E., Samineni, Laxmicharan, Lang, Chao, Thokkadam, Alina, Carson, Drew, Dai, Yuxuan, Mukthar, Arwa, Zhang, Miaoci, Parshin, Andrey, Sloand, Janna N., Medina, Scott H., Grzelakowski, Mariusz, Bhattacharya, Dibakar, Phillip, William A., Gomez, Enrique D., Hickey, Robert J., Wei, Yinai, and Kumar, Manish
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- 2020
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5. EU Transport Modal Shift Versus the Regulatory Requirements for Transport Sector's Green Transformation Towards Climate Neutrality.
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Grzelakowski, Andrzej S.
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- 2024
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6. Transport Systems and their Impact on Trade Facilitation, Logistics Performance and Competitiveness: An Analytical Approach.
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Grzelakowski, Andrzej S.
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- 2024
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7. Global Maritime Container Carriers' Mid-term Strategies as a Tool for Change Management in the Post-Covid Era.
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Grzelakowski, Andrzej S.
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- 2023
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8. Costs and Benefits of the Disruptions Caused by the Pandemic Crisis and the Container Shipping Market’s Turbulences and their Allocation within the Global Supply Chains: An Analytical Approach.
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Grzelakowski, Andrzej S.
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- 2023
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9. Global Container Shipping Operators' Strategies Under the Extremely Turbulent Market Dynamic Environment: An Analytical Approach.
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Grzelakowski, Andrzej S.
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- 2022
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10. Extended-Duration Betrixaban Reduces the Risk of Stroke Versus Standard-Dose Enoxaparin Among Hospitalized Medically Ill Patients
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Legkonogov, O., Ramacciotti, E., Mikhailova, E., Koryk, V., Adzerikho, I., Schoenerr, H., Mathies, R., Konig, J., Huber, K., Rubinfeld, A., Finfer, S., Manenti, E., Bott, M., Blessing, E., Beyer-Westendorf, J., Coughlin, P., Baker, R., Poy, C., Dengler, T., Parody, M., Oliva, M., Macin, S., Jure, H., Ferrari, A. E., Dziewas, R., Genth-Zotz, S., Hamann, F., Horacek, T., Klimpe, S., Mitkovskaya, N., Kroning, R., Lapp, H., Lawall, H., Licka, M., Rizos, T., Tiefenbacher, C., Weimar, C., Alkonyi, B., Falukozy, J., Futo, L., Katona, A., Berrouschot, J., Kirschner, R., Amann, B., Paposhvili, K., Pagava, Z., Kristof, P., Lakatos, F., Laszlo, Z., Freire, A., Lupkovics, G., Megreladze, I., Kobulia, B., Khintibidze, I., Khabeishvili, G., Datikashvili-David, I., Simoneau, G., Merkely, B., Andras, C. Nagy, Nemeth, L., Papp, A., Soltesz, P., Fiss, E., Schmidt, J., Roy, P-M., Quere, I., Proust, A., Pottier, P., Pernod, G., Payot, L., Bizzacchi, J. Annichino, Lienart, F., Paleiron, N., Montaclair, K., Mismetti, P., Messas, E., Lacroix, P., Grange, C., Falvo, N., El Kouri, D., Decoulx, E., Debourdeau, P., De Geeter, G., Brisot, D., Belhassane, A., Aquilanti, S., Agraou, B., Vikman, S., Tatlisumak, T., Saarinen, J., Kaaja, R., Honkaniemi, J., Airaksinen, J., Uuetoa, T., Lember, M., Urhammer, S., Tuxen, C., Storgaard, M., Lassen, M., Christensen, H., Vyhnanek, M., Vejvoda, J., Spacek, R., Reiterer, P., Podpera, I., Mikulova, J., Lang, P., Jajtner, P., Hubac, J., Horny, I., Holaj, R., Herold, M., Havelka, J., Francek, L., Dusek, J., Dunaj, M., Cizek, V., Chochola, J., Chlumsky, J., Cermak, O., Skerk, V., Vagic, J. Sikic, Marusic, S., Knezevic, A., Kalinic-Grgorinic, H., Jakopovic, M., Francetic, I., Ciglenecki, N., Car, S., Butkovic-Soldo, S., Cardenas, S. Potthoff, Lazcano, M. Opazo, Alarcon, M. Arias, Verreault, S., Provencher, S., Pearce, M., Le Gal, G., Douketis, J., Dhar, A., Tokmakova, M., Todorov, G., Syulemzova, S., Raymuno, S., Rocha, A., Dimov, B., Grigorov, M., Kalpachki, R., Kamenova, Z., Bello, F., Harrington, Robert A., Bandman, Olga, Kostadinova, M., Milanova, M., Dive, A., Pencheva, G., Sudar, Z., Szabo, G., Szegedi, N., Timar, G., Valco, J., Delforge, M., Vertes, A., Efrati, S., Elias, M., Gafter, A., Nazliel, BİJEN, Hayek, T., Hussein, O., Lishner, M., Lugassy, G., Cerveri, I., D'Angelo, A., De Pellegrin, A., Imberti, D., Landolfi, R., Runev, N., Lembo, G., Lodigiani, C., Moia, M., Molteni, M., Mumoli, N., Novo, S., Orlandini, F., Stoeva, N., Parisi, R., Pizzini, A., Pomero, F., Salvi, A., Schenone, A., Gold, Alex, Visona, A., Martinova, V., Pontaga, N., Rozitis, V., Stukena, I., Alekniene, B., Basijokiene, V., Butkiene, Z., Griskeviciene, V., Naudziunas, A., Stoyanov, M., Norvaisiene, R., Norviliene, R., Petrauskiene, R., Poskiene, R., Susinskiene, D., Valavicius, A., Castillo Leon, R., Pimanov, S., Polonetsy, L., Pereyra, R. Cotrina, Karlo, L. Farjardo, Horna, M., Soroka, N., Salas, M., Yanez, L. Toche, Fryze, W., Gaciong, Z., Gniot, J., Gorecka, D., Gruenpeter, P., Grzelakowski, P., Jastrzebski, D., Kucharski, L., Mirek-Bryniarska, E., Pulkowski, G., Sobkowicz, B., Sulik, P., Walasek, L., Blockmans, D., Waldemar, K., Wrzesinski, K., Balogh, Z. E., Bojinca, M., Marin, I., Musetescu, R., Podoleanu, C., Popescu, M., Stamate, S., Stanciulescu, G., Vida-Simiti, L., Abashev, A., Andreev, D., Apartsin, K., Arkhipov, M., Averkov, O., Barbarash, O., Belskaya, G., Bogdanov, E., Boldueva, S., Chefranova, Z., Dovgalevskiy, Y., Ershova, O., Goloshchekin, B., Khachatryan, N., Klein, G., Kobalava, Z., Kosmacheva, E., Kostenko, V., Malygin, A., Martynenko, T., Martynenko, V., Maslova, N., Mordovin, V., Nikolaev, K., Nilk, R., Popov, D., Privalova, E., Reshetko, O., Shapovalova, Y., Shpagina, L., Shvarts, Y., Simanenkov, V., Solovyov, O., Vishneva, E., Vishnevskiy, A., Apostolovic, S., Celic, V., Ilic, S., Kovacevic-Kuzmanovic, A., Miloradovic, V., Bodikova, S., Cervenakova, A., Dvorak, M., Herman, O., Hrubon, A., Kokles, M., Krastev, G., Payer, J., Prokop, D., Spisakova, M., Adler, D., Basson, M., Breedt, J., Engelbrecht, J., Mitha, I., Van Dyk, C., Alvarez Sala, L. A., Barbagelata Lopez, C., Bisbe, J., Castro Guardiola, A., Cepeda, J. M., Cereto, F., Diaz Santos, E., Ferrer, R., Gomez Cerezo, J., Hernandez, Adrian F., Gonzales-Porras, J. R., Grandes, J., Cohen, Alexander T., Gibson, C. Michael, Chi, Gerald, Halaby, Rim, Korjian, Serge, Daaboul, Yazan, Jain, Purva, Arbetter, Douglas, Goldhaber, Samuel Z., Hull, Russel, Jimenez, D., Mellibovsky, L., Richart, C., Riera, A., Trujillo, J., Vargas Nunez, J. A., Villalta, J., Akgul, O., Guneri, S., Kilichesmez, K., Kirma, C., Kutluk, H., Okumus, G., Tigen, K., Topcuoglu, M., Tuncay, E., Abrahamovych, O., Batushkin, V., Brozhyk, J., Burmak, I., Godlevska, O., Goloborodko, A., Goloborodko, B., Goncharova, Y., Gryb, V., Karpenko, O., Kopytsya, M., Zakai, N., Yousef, K., Wichman, T., Whitman, B., Welker, J., Welch, M., Warner, A., Updegrove, J., Tuck, M., Stoltz, S., Sokol, S., Sharma, S., Shammas, N., Saba, F., Rodriguez, W., Rees, C., Rastogi, P., Rajan, R., Quintana, O., Pullman, J., Pratt, R., Pineda, L., Pearl, R., Parthiban, K., Overcash, J., Ortel, T., Ohaju, V., Nadar, V., Mittal, M., Milling, T., McLaren, G., Margolis, B., Mahal, S., Macchiavelli, A., Lopez, J., Lerner, R., Kung, M., Kouras, F., Kazimir, M., Kao, C-K., Kabler, H., Ioachimescu, O., Hazelrigg, M., Hamad, A., Haidar, A., Hahn, B., Goytia-Leos, D., Gaggin, H., Fulmer, J., Koshlia, V., Fraiz, J., Krakhmalova, O., Fermann, G., Farley, B., Doshi, A., Dhingra, R., Cornell, J., Concha, M., Clark, C., Chang, H., Carman, T., Bidair, M., Bercz, P., Bastani, A., Barney, J., Baker, S., Anderson, C., Amin, M., Almasri, E., Natarajan, I., McCollum, C., MacCallum, P., Davis, M., Body, R., Yagensky, A., Voronkov, L., Vishnivestsky, I., Vakaliuk, I., Ursol, G., Tseluyko, V., Kyrychenko, I., Svyshchenko, Y., Svyridova, I., Ryabichenko, T., Rudenko, L., Reshotko, D., Perepeliuk, M., Parkhomenko, O., Nikonov, V., Maslovaskyi, V., Malynovsky, Y., Sergeeva, E., and Kolman, P.
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Male ,medicine.medical_specialty ,Pyridines ,Intracranial Hemorrhages ,030204 cardiovascular system & hematology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Medical illness ,Physiology (medical) ,medicine ,Humans ,030212 general & internal medicine ,Enoxaparin ,Intensive care medicine ,Stroke ,Aged ,business.industry ,Anticoagulants ,Venous Thromboembolism ,medicine.disease ,Thrombosis ,chemistry ,Betrixaban ,Benzamides ,Emergency medicine ,Female ,Cardiology and Cardiovascular Medicine ,business ,Complication ,Venous thromboembolism - Abstract
Background: Stroke is a morbid and potentially mortal complication among patients hospitalized with acute medical illness. The potential of extended-duration thromboprophylaxis with the factor Xa inhibitor betrixaban to reduce the risk of stroke compared with standard-dose enoxaparin in this population was assessed in this retrospective APEX trial substudy (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban). Methods: Hospitalized acutely medically ill subjects (n=7513) were randomized in a double-dummy double-blind fashion to either extended-duration oral betrixaban (80 mg once daily for 35–42 days) or standard-dose subcutaneous enoxaparin (40 mg once daily for 10±4 days) for venous thromboprophylaxis. Stroke events were adjudicated by an independent, blinded event adjudication committee. Results: The mean age of study participants was 76 years; 45% were male; 13% had had a stroke; and 45% had congestive heart failure. There were fewer all-cause strokes (0.54% versus 0.97%; relative risk [RR]=0.56; 95% confidence interval, 0.32–0.96; P =0.032; adjusted RR=0.43%; number needed to treat=233) and ischemic strokes (0.48% versus 0.91%; RR=0.53; 95% confidence interval, 0.30–0.94; P =0.026; adjusted RR=0.43%; number needed to treat=233) among patients treated with betrixaban versus enoxaparin through 77 days of follow-up. Among high-risk subjects, those with congestive heart failure or ischemic stroke as their index event, betrixaban reduced the risk of all-cause stroke (0.72% versus 1.48%; RR=0.49; 95% confidence interval, 0.26–0.90; P =0.019; adjusted RR=0.76%; number needed to treat=132) and ischemic stroke (0.63% versus 1.38%; RR=0.45; 95% confidence interval, 0.24–0.87; P =0.014; adjusted RR=0.75%; number needed to treat=134) compared with enoxaparin. Conclusions: Among hospitalized medically ill patients, extended-duration betrixaban significantly reduced all-cause stroke and ischemic stroke through 77 days of follow-up Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01583218.
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- 2017
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11. Maritime Container Terminal Process Maturity: A Methodological Approach and Empirical Evidence.
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Charłampowicz, Jędrzej and Grzelakowski, Andrzej S.
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- 2022
12. A Multicenter, Phase 2, Randomized, Placebo-Controlled, Double-Blind, Parallel-Group, Dose-Finding Trial of the Oral Factor XIa Inhibitor Asundexian to Prevent Adverse Cardiovascular Outcomes After Acute Myocardial Infarction
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Rao, Sunil V., Kirsch, Bodo, Bhatt, Deepak L., Budaj, Andrzej, Coppolecchia, Rosa, Eikelboom, John, James, Stefan K., Jones, W. Schuyler, Merkely, Bela, Keller, Lars, Hermanides, Renicus S., Campo, Gianluca, Ferreiro, José Luis, Shibasaki, Taro, Mundl, Hardi, Alexander, John H., Hengstenberg, Christian, Steinwender, Clemens, Alber, Hannes, Steringer-Mascherbauer, Regina, Schober, Andreas, Auer, Johann, Roithinger, Franz Xaver, von Lewinski, Dirk, Moertl, Deddo, Huber, Kurt, Coussement, Patrick, Hoffer, Etienne, Beauloye, Christophe, Janssens, Luc, Vranckx, Pascal, De Raedt, Herbert, Vanassche, Thomas, Vrolix, Matthias, Rokyta, Richard, Parenica, Jiri, Pelouch, Radek, Motovska, Zuzanna, Alan, David, Kettner, Jiri, Polasek, Rostislav, Cermak, Ondrej, Sedlon, Pavel, Hanis, Jiri, Novak, Martin, Belohlavek, Jan, Horacek, Thomas, Leggewie, Stefan, Wenzel, Philip, vom Dahl, Juergen, Sievers, Burkhard, Pulz, Jan, Schellong, Sebastian, Clemmensen, Peter, Muller-Hennessen, Matthias, Rassaf, Tienush, Falukozi, Jozsef, Ruzsa, Zoltan, Tomcsanyi, Janos, Csanadi, Zoltan, Herczeg, Bela, Koszegi, Zsolt, Vorobcsuk, Andras, Kiss, Robert, Baranyai, Csaba, Dezsi, Csaba, Merkely, Bela, Lupkovics, Geza, Rossini, Roberta, Scherillo, Marino, Sergio Saba, Pier, Calogero Campo, Gianluca, Calo, Leonardo, Nassiacos, Daniele, Quadri, Giorgio, Sciahbasi, Alessandro, Silvio Marenzi, Gian Carlo, Reimers, Bernhard, Perna, Gian Piero, Sacca, Salvatore, Fattore, Luciano, Brunelli, Claudio, Picchi, Andrea, Kuramochi, Takehiko, Kondo, Kazuhisa, Aoyama, Takahiko, Kudoh, Takashi, Yamamoto, Tadashi, Takaya, Tomofumi, Mukai, Yasushi, Fukui, Kazuki, Morioka, Nobuyuki, Ando, Kenji, Yamamuro, Atsushi, Morita, Yasuhiro, Koga, Yasuaki, Watanabe, Tetsuya, Sakamoto, Tomohiro, Shibasaki, Taro, Maebuchi, Daisuke, Takahashi, Akihiko, Yonetsu, Taishi, Kakuta, Tsunekazu, Nishina, Hidetaka, Oemrawsingh, Rohit, Dorman, Reinhart, Oude Ophius, Ton, Prins, Paco, al Windy, N.Y.Y., Zoet-Nugteren, S.K., Hermanides, Rik, van Eck, Martijn, Scherptong, Roderick, Cornel, J.H., Damman, Peter, Bech, Gerhard, Torquay, R., Kietselaer, Bas, Grzelakowski, Pawel, Krzysztof, Dyrbus, Budaj, Andrzej, Miekus, Pawel, Przybylski, Andrzej, Zarebinski, Maciej, Balsam, Pawel, Szachniewicz, Joanna, Gierlotka, Marek, Tycinska, Agnieszka, Iniguez Romo, Andres, Fernandez Ortiz, Antonio, Carrasquer Cucarella, Anna, Sanmartin Fernandez, Marcelo, Sionis, Alessandro, Bueno Zamora, Hector, Ferreiro Gutierrez, Jose Luis, Almenar, Luis, Ferreira Gonzalez, Ignacio, Pascual Figal, Domingo A., Almendro Delia, Manuel, Jimenez Fernandez, Miriam, Skeppholm, Mika, Zedigh, Crister, Angeras, Oskar, Lauermann, Jorg, Erlinge, David, Gustafsson, Robin, Mooe, Thomas, Utreras, Alejandro, James, Stefan, Grimfjard, Per, Pedrazzini, Giovanni, Mach, Francois, Fournier, Stephane, Haegeli, Laurent, Beer, Jurg H., Leibundgut, Gregor, Kobza, Richard, Kaiser, Christoph, Kunadian, Vijay, Al-Lamee, Rasha, Gorog, Diana, Khan, Sohail, Trevelyan, Jasper, Toor, Iqbal, Smith, James, Purushottam, Bhaskar, Treasure, Charles, Arena, Frank, Vedere, Amarnath, Henderson, David, Gilani, Syed, Jones, Alonzo, Carrillo-Jimenez, Rodolfo, Gillespie, Eve, Marhefka, Gregary, Wang, David, Olson, Charles, Bloom, Stephen, Iftikhar, Faizan, Brabham, David, McGinty, John, Thompson, Charles, Talano, James, Ginete, Wilson, Williams, Marcus, Masud, Ali, Ariani, Mehrdad, Bitar, Fahed, Wang, Thomas, and Samuelson, Bradley
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- 2022
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13. Physicians' guideline adherence is associated with long-term heart failure mortality in outpatients with heart failure with reduced ejection fraction: the QUALIFY international registry
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Komajda, M. Schöpe, J. Wagenpfeil, S. Tavazzi, L. Böhm, M. Ponikowski, P. Anker, S.D. Filippatos, G.S. Cowie, M.R. Aleksanyan, A. Atayan, L. Avetisyan, A. Davtyan, N. Drambyan, M. Gevorgyan, K. Grigoryan, M. Hakobyan, Z. Hayrapetyan, H. Kocharyan, L. Kramarevskaya, T. Melqonyan, A. Muradyan, F. Nanyan, R. Ordyan, A. Ordyan, M. Piruzyan, A. Podosyan, G. Safaryan, K. Sargsyan, T. Sarkisyan, A. Sisakyan, H. Ter-Grigoryan, V. Ustyan, T. Alexopoulos, C. Amerena, J. Arstall, M. Ayres, B. Barron, G. Beltrame, J. Bou-Samra, J. Brown, M. Cross, D. Dwyer, N. Eccleston, N. Hare, D. Ho, B. Hopper, I. Jackson, B. Korczyk, D. Lattimore, J.D. Levendel, A. Macfadyen, R. Pandeli, V. Playford, D. Richardson, M. Senior, J.A. Shah, A. Shetty, P. Soward, A. Srivastava, P. Swale, M. Vogl, E. Wai, B. William, M. Worthington, A. Wright, S. Brunner, B. Fuhrmann, W. Horer, L. Maca, T. Nahler, A. Ortner, H. Racz, G. Scheibner, P. Sebald, C. Abdullayev, A. Abdullayev, R. Ahmadov, A. Alakbarov, E. Aliyev, F. Aliyev, F. Bakhshaliyev, A. Bakhshiyev, M. Dadashova, G. Dashdamirov, R. Faradjova, N. Guliyev, A. Guliyev, F. Guliyeva, S. Hajiyev, G. Ibrahimov, F. Imanov, G. Isayeva, A. Isayeva, M. Jabrailova, U. Jafarov, R. Jahangirov, T. Khalilov, A. Khalilov, S. Mehdiyev, S. Najafov, R. Samedova, H. Shahhuseynov, S. Yusifly, R. Yusifov, T. Zahidova, K. Zeynalov, A. Abdullatif, A. Al-Banna, R. Haiky, W. Husain, A. Jamsheer, A. Barbuk, O. Belskaya, M. Borodko, V. Kurlianskaya, A. Mackevich, S. Mankevich, N. Moroz-Vodolazhskaya, N. Ravtovich, O. Saevich, A. Troyanova, T. Chughtai, A. Johar, S. Luqman, N. Nair, T.C.-R. Deyoung, P. Ezekowitz, J. Frenette, M. Howlett, J. Huynh, T. Nguyen, V. Toma, M. Orenstein, T. Rinne, M.R.C. Virani, S. Zieroth, S. Ailiman, M. Cong, H. Ding, W. Dong, W. Dong, Y. Gao, C. Li, L. Li, Z. Liang, Y. Liu, X. Liu, S. Luo, S. Shi, H. Tian, Q. Wang, D. Wang, J. Wei, M. Wu, C. Xu, D. Yang, X. Yang, Z. Zhang, C. Zhang, Q. Zhang, Y. Zhang, R. Zheng, Y. Zhao, L. Zhou, J. Buch, P. Davidsen, F. Eiskjær, H. Bruun, N.E. Kragh-Thomsen, N.E. Franow, H. Køber, L. Korup, E. Madsen, B.K. Mikkelsen, K. Nielsen, K.A. Nørgaard, A. Refsgaard, J. Rickers, H. Kaiser, P. Sykulski, R. Zeuthen, E.L. El Fottoh, A.A. El Badry, M. El Hady, Y.A. El Kady, E. El Khatib, H. Fawzy, M. Hegazy, H. Salama, M.K. Mortada, A. Mostafa, T. Mwafy, A. Ossama, M. Samir, S. Seleem, M. Sobhy, B. Bregadze, G. Chelidze, K. Chumburidze, V. Jalabadze, K. Khabeishvili, G. Kiphiani, Z. Klimiashvili, Z. Kvitsiani, A. Mamatsashvili, M. Melia, I.M.A. Oragvelidze, T. Orjonikidze, S. Paposhvili, K. Petriashvili, S. Phaghava, Z. Shushania, M. Tsetskhladze, E. Tsinamdzgvishvili, B. Abdel-Qader, M. Al-Zoebi, A. Böhm, G. Bosch, R. Brune, S. Bunge, K. Dominick, K. Duda, S. Erdogan, A.E. Faber, G. Fach, C. Fechtrup, C. Frickel, S. Giokoglu, K. Haas, J. Hagenow, A. Haj-Yehia, A. Hansen, C. Hartung, W.M. Hauser, E.R. Hofmeister, A. Hohensee, H. Hüttemann, M. Keim, M. Krämer, A. Langwasser, K. Lodde, B.P. Lorch, G. Lüer, C. Müller, K. Placke, J. Plesch, B. Potolidis, L. Richter, F. Rieker, W.A. Schlichting, J. Stenzel, G. Theuer, J.D. Marcin, A. Warkentin, R. Wegner, M. Wilke, A. Agrafiotis, I. Aleksandridis, I. Farmakis, D. Giannakoulas, G. Karavidas, A. Lamprou, A. Ninios, V. Panagiotopoulos, K. Papadopoulos, K. Siachos, S. Dékány, M. Borbéy, A. Borsányi, T. Forster, T. Gavallér, H. Gyuricza, I. Heltai, K. Herczeg, B. HŐgye, M. Losonczi, I. Merkely, B. Metz, E. Muk, B. Nagy, K. Ökrös, M. Piry, K. Poós, G. Sárszegi, Z. Somogyi, T. Sziliczei-Németh, E. Tátrai, T. Zima, E. Zsigmond, A. Daly, C. Mahon, N. Meany, B. Abbdi, I. Awaysheh, R. Azouka, M. Hamoudeh, S. Nammas, A. Okkeh, O. Aimakova, G. Ismagulova, Z. Issabekova, A. Junusbekova, G.A. Koshumbayeva, K. Madaliyev, K. Mekebekova, D. Mukatova, A. Ospanova, G. Sadvakassova, G. Sunkarbekova, Z. Yegorova, Y. Zhangelova, S. Kim, K.H. Al-Mutairi, M. Gaber, Y. Ghali, I. Ghanem, A. Hafez, H. Haiba, M. Koushy, T. Mahmoud, A. Raafat, G. Sallam, M. Senousi, O. Soliman, M. Massih, T.A. Ali, S.A. Jaoude, S.A. Azzi, N. Badaoui, G. Bayeh, H. Beydoun, A. Chammas, E. Dib, H. Gebran, M. Ghanem, G. Haidar, H. Hamadeh, M. Hamoui, O. Hobeika, R. Jazra, C. Kabbani, S. Kadri, Z. Karanaminassian, R. Kassab, R. Kleit, M. Mansour, H. Mousallem, N. Semaan, C. Simonian, A. Sarkis, A. Succar, S. Zalloum, R. Zind, R. Anusauskiene, J. Grigaliuniene, A. Karaliute, R. Kavoliuniene, A. Kozlovaite, V. Miliuniene, D. Rinkuniene, D. Rudys, A. Stasaityte, D. Aziz, F.A.A. Rahim, A.A.A. Ahmad, R. Ahmadsah, S.H.K.A. Ang, C.C. Ang, S.H. Cham, Y.L. Chee, K.H. Chooi, K.C. Chu, C.M. Fam, T.L. Fong, A. Ismail, O. Ismail, J.R. Kamarulzaman, M.H. Kasim, S.S. Khiew, N.Z. Krishnan, C. Krishinan, S. Lau, G. Lee, L.Y. Liew, H.B. Lim, C.W. Mahendran, K. Dass, R.D.M. Mohamad, R. Arshad, M.K.M. Unit, H.M. Mustapha, Z. Ng, W.K. Ong, T.K. Oon, Y.Y. Ramli, A.W. Ramanathan, G.R.L. Ross, N.T. Said, A. Sarwar, M. Tan, E. Tan, S.K. Voon, C.Y. Yusoff, M.R. Abidin, H.A.Z. Chua, S.K. Yew, K.L. Amin, N.H.M. Kandiah, K. Chong, L.A. Mohamed, M.S. Lim, B.K. Koh, K.T. Low, D.W. Abdelkhirane, C. Allali, Y. Askour, M. Balafrej, K. Bendagha, N. Bendriss, L. Benjelloun, H. Chaib, A. Cherradi, G. Cherti, M. Chtioui, M. El Belghiti, A.R. Fihri, O.F. Habbal, R. El Hattaoui, M. Khatouri, A. Kheyi, J. Kriem, J. Soufiane, N. Soufiani, A. Zaimi, S. Adamczyk-Kot, D. Barg, Z. Bartkowiak, R. Braciszewicz, W. Czajkowska, E. Dudek-Niechciał, M. Grzelakowski, P. Jarosik, Z. Jerzykowska, O. Koprowski, P. Krysiak, W. Łajkowski, Z. Ziemlewska-Krawczyk, E. Lelonek, M. Lewicka, E. Płonka, J. Sadowski, J. StĘpieŃ-Adamczewska, V. Szponar, J. WrzesiŃski, K. Brito, D.A. Araújo, I. Figueiredo, J.P.A. Campelo, M.B. Sardinha, P.M.B. Fernando, P. de Brito Domingues Sanches Peres de Noronha, M.A. Baptista, S.B.C. Cardoso Pinto, J.P. Piçarra, B.M.C. Farto e Abreu, P. da Fonseca, M.C.F.G. Soares, A.I.C.G.O. Resende, J.D.A. Durão, D.L. Nascimento, A.I.F.V. Bernardes, E.L.M.O. Marques, F. Ramos, M.A.N. Sargento, L.J.M. dos Santos, J.P.F. Raimundo, A. da Luz Ventosa, A.M.S. Sarmento, P. Aguiar, C.M.T. Ahmed, E. Al-Suwaidi, J. Al Dabdoob, W. Badr, A. Gomaa, M. Albu, M. Antohi, I. Apavaloaei, C. Ardelean, A. Badea, G. Bicescu, G. Blaj, C. Bogdan, L. Bucatanschi, M. Buzea, A. Calarasu, V. Catinean, S. Christodorescu, R. Cocoi, D. Costache, L. Cretu, D. Crisu, D. Dima-Cozma, C. Dumitrescu, S. Enache, V. Firastrau, V. Frigy, A. Gherghina, A. Girbea, S. Gutu, A. Horovitz, M. Hortopan, G. Istratoaie, O. Jianu, C. Jinga, L. Lighezan, D. Luka, A. Magheru, S. Mercea, D. Miklos, K. Moga, R. Oprea, N. Paraschiv, D.M. Pop, D. Rusu, R. Sirbu, I. Socoteanu, E. Stanciulescu, G. Suteu, A. Tetiu, O. Traistaru, A. Tudoran, M. Turiceanu, M.C. Viinkler, L. Adonina, E. Akinina, S. Alferov, P. Arkhipov, M. Aroutunov, G. Babkin, A. Barbashina, T. Bochkareva, J. Boldueva, S. Bukhonkina, J. Chumakova, S.G. Fayans, I. Furmenko, G. Galyavich, A. Grinstein, Y. Klein, G. Kastanayan, A. Kazachkova, T. Korolev, S. Koshelskaya, O. Kosmacheva, E. Koziolova, N. Kuimov, A. Kushnarenko, N. Lebedev, P. Matushin, G. Mineeva, E. Motylev, I. Nedbaykin, A. Nevzorova, V. Rachkova, S. Rebrov, A. Reznik, I. Saiganov, S. Sayfutdinov, R. Schekotov, V. Serdechnaya, E. Shalaev, S. Shtegman, O. Sitnikova, M. Smolenskaya, O. Sulimov, V. Tarlovskaya, E. Temnikova, E. Timonin, D. Tolstov, S. Uskatch, T. Ustyuzhanin, V. Valeeva, R. Vasyuk, Y. Viktorova, I. Yakushin, S. Zadionchenko, V. Zateischikov, D. Zhirov, I. Bollová, D. Dulková, K. Fazekaš, F. Hermel, I. KŇazeje, M. NedĚĽová, I. Nociar, J. Procházka, L. Pundová, L. Slanina, M. Varga, I. Almenar, L. Beltrán, P. Cobo, M. Delgado, J. Enjuanes, C. Garrido, I. Gómez, M.A. Manito, N. Marzal, D. Murga, N. Ocampo, M. Pérez, J. Sánchez, I. Buakhamsri, A. Leemasawat, K. Kanoksilp, A. Kiatchoosakun, S. Phrommintikul, A. Porapakkham, P. Rodprasert, S. Senthong, V. Wongcharoen, W. Wongwantanee, S. Bahadir, H. Emül, A. Gokce, M. Gurcagan, A. Kaya, O.K. Keser, A. Pinar, P. Taș, M.H. Tosun, H.B. Yazlar, A.S. Yilmaz, S. Yuksel, Y. Bagriy, A. Ivchyna, N. Lyashenko, A. Matviychuk, N. Shchukina, O. Tkach, N. Tseluyko, V. Vasylieva, L. Abdallah, A. Agrawal, A. Basleeb, F. Bazargani, N. Hatou, E. Al Kaddour, A.R. Al Kasser, M. Al Mulla, A. Radaideh, G. Salustri, A. on behalf of the QUALIFY Investigators
- Abstract
Background: Physicians' adherence to guideline-recommended therapy is associated with short-term clinical outcomes in heart failure (HF) with reduced ejection fraction (HFrEF). However, its impact on longer-term outcomes is poorly documented. Here, we present results from the 18-month follow-up of the QUALIFY registry. Methods and results: Data at 18 months were available for 6118 ambulatory HFrEF patients from this international prospective observational survey. Adherence was measured as a continuous variable, ranging from 0 to 1, and was assessed for five classes of recommended HF medications and dosages. Most deaths were cardiovascular (CV) (228/394) and HF-related (191/394) and the same was true for unplanned hospitalizations (1175 CV and 861 HF-related hospitalizations, out of a total of 1541). According to univariable analysis, CV and HF deaths were significantly associated with physician adherence to guidelines. In multivariable analysis, HF death was associated with adherence level [subdistribution hazard ratio (SHR) 0.93, 95% confidence interval (CI) 0.87–0.99 per 0.1 unit adherence level increase; P = 0.034] as was composite of HF hospitalization or CV death (SHR 0.97, 95% CI 0.94–0.99 per 0.1 unit adherence level increase; P = 0.043), whereas unplanned all-cause, CV or HF hospitalizations were not (all-cause: SHR 0.99, 95% CI 0.9–1.02; CV: SHR 0.98, 95% CI 0.96–1.01; and HF: SHR 0.99, 95% CI 0.96–1.02 per 0.1 unit change in adherence score; P = 0.52, P = 0.2, and P = 0.4, respectively). Conclusion: These results suggest that physicians' adherence to guideline-recommended HF therapies is associated with improved outcomes in HFrEF. Practical strategies should be established to improve physicians' adherence to guidelines. © 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology
- Published
- 2019
14. Comparison of Fatal or Irreversible Events With Extended-Duration Betrixaban Versus Standard Dose Enoxaparin in Acutely III Medical Patients: An APEX Trial Substudy
- Author
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Gibson, C. M., Korjian, S., Chi, G., Daaboul, Y., Jain, P., Arbetter, D., Goldhaber, S. Z., Hull, R., Hernandez, A. F., Lopes, R. D., Gold, A., Cohen, A. T., Harrington, R. A., Bello, F., Ferrari, A. E., Jure, H., Macin, S., Oliva, M., Parody, M., Poy, C., Baker, R., Colquhoun, D., Coughlin, P., Finfer, S., Hammerschlag, G., Rubinfeld, A., Huber, K., Konig, J., Mathies, R., Pilger, E., Schoenerr, H., Adzerikho, I., Koryk, V., Mikhailova, E., Mitkovskaya, N., Pimanov, S., Polonetsy, L., Soroka, N., Blockmans, D., Delforge, M., Dive, A., Lienart, F., Motte, S., Annichino Bizzacchi, J., Fiss, E., Freire, A., Manenti, E., Ramacciotti, E., Raymuno, S., Rocha, A., Saraiva, J. F., Dimov, B., Grigorov, M., Kalpachki, R., Kamenova, Z., Kostadinova, M., Milanova, M., Mincheva, V., Pencheva, G., Raev, D., Runev, N., Stoeva, N., Stoyanov, M., Syulemzova, S., Todorov, G., Tokmakova, M., Dhar, A., Douketis, J., Kahn, S., Le Gal, G., Pearce, M., Provencher, S., Verreault, S., Arias Alarcon, M., Olivares Canon, C., Opazo Lazcano, M., Potthoff Cardenas, S., Butkovic-Soldo, S., Car, S., Ciglenecki, N., Francetic, I., Jakopovic, M., Kalinic-Grgorinic, H., Knezevic, A., Malojcic, B., Marusic, S., Sikic Vagic, J., Skerk, V., Cermak, O., Cervinka, P., Chlumsky, J., Chochola, J., Cizek, V., Dunaj, M., Dusek, J., Francek, L., Havelka, J., Herold, M., Holaj, R., Horny, I., Hubac, J., Jajtner, P., Kolman, P., Lang, P., Mayer, O., Mikulova, J., Podpera, I., Reiterer, P., Spacek, R., Vejvoda, J., Vyhnanek, M., Christensen, H., Lassen, M., Storgaard, M., Tuxen, C., Urhammer, S., Lember, M., Marandi, T., Uuetoa, T., Airaksinen, J., Honkaniemi, J., Kaaja, R., Lassila, R., Saarinen, J., Tatlisumak, T., Vikman, S., Agraou, B., Aquilanti, S., Belhassane, A., Brisot, D., De Geeter, G., Debourdeau, P., Decoulx, E., El Kouri, D., Falvo, N., Grange, C., Lacroix, P., Messas, E., Mismetti, P., Montaclair, K., Mottier, D., Paleiron, N., Payot, L., Pernod, G., Pottier, P., Proust, A., Quere, I., Roy, P. -M., Schmidt, J., Simoneau, G., Datikashvili-David, I., Khabeishvili, G., Khintibidze, I., Kobulia, B., Megreladze, I., Pagava, Z., Paposhvili, K., Shaburishvili, T., Amann, B., Berrouschot, J., Beyer-Westendorf, J., Blessing, E., Bott, M., Dengler, T., Diehm, C., Dziewas, R., Genth-Zotz, S., Hamann, F., Horacek, T., Klimpe, S., Kroning, R., Lapp, H., Lawall, H., Licka, M., Rizos, T., Schellong, S., Schmidt-Lucke, J., Singer, C., Tiefenbacher, C., Veltkamp, R., Weimar, C., Zeymer, U., Alkonyi, B., Falukozy, J., Futo, L., Katona, A., Kirschner, R., Kristof, P., Lakatos, F., Laszlo, Z., Lupkovics, G., Merkely, B., Nagy Andras, C., Nemeth, L., Papp, A., Soltesz, P., Sudar, Z., Szabo, G., Szegedi, N., Timar, G., Valco, J., Vertes, A., Efrati, S., Elias, M., Gafter, A., Hayek, T., Hussein, O., Lishner, M., Lugassy, G., Zeltser, D., Ageno, W., Cerveri, I., D'Angelo, A., De Pellegrin, A., Imberti, D., Landolfi, R., Lembo, G., Lodigiani, C., Luisetti, M., Moia, M., Molteni, M., Mumoli, N., Novo, S., Orlandini, F., Parisi, R., Pizzini, A., Pomero, F., Salvi, A., Schenone, A., Visona, A., Krievins, D., Martinova, V., Pontaga, N., Rozitis, V., Stukena, I., Alekniene, B., Bagdonas, A., Basijokiene, V., Butkiene, Z., Griskeviciene, V., Naudziunas, A., Norvaisiene, R., Norviliene, R., Petrauskiene, R., Poskiene, R., Susinskiene, D., Valavicius, A., Castillo Leon, R., Cotrina Pereyra, R., Farjardo Karlo, L., Horna, M., Lema Osores, J., Salas, M., Toche Yanez, L., Fryze, W., Gaciong, Z., Gniot, J., Gorecka, D., Gruenpeter, P., Grzelakowski, P., Jastrzebski, D., Kucharski, L., Mirek-Bryniarska, E., Pulkowski, G., Sobkowicz, B., Sulik, P., Tomkowski, W., Walasek, L., Waldemar, K., Wrzesinski, K., Balogh, Z. E., Bojinca, M., Marin, I., Mot, S., Musetescu, R., Podoleanu, C., Popescu, M., Stamate, S., Stanciulescu, G., Vida-Simiti, L., Abashev, A., Andreev, D., Apartsin, K., Arkhipov, M., Averkov, O., Barbarash, O., Belskaya, G., Bogdanov, E., Boldueva, S., Chefranova, Z., Dovgalevskiy, Y., Ershova, O., Goloshchekin, B., Khachatryan, N., Khurs, E., Klein, G., Kobalava, Z., Kosmacheva, E., Kostenko, V., Malygin, A., Martynenko, T., Martynenko, V., Maslova, N., Mordovin, V., Nikolaev, K., Nilk, R., Panchenko, E., Popov, D., Privalova, E., Reshetko, O., Sergeeva, E., Shapovalova, Y., Shpagina, L., Shvarts, Y., Simanenkov, V., Solovyov, O., Vishneva, E., Vishnevskiy, A., Apostolovic, S., Celic, V., Ilic, S., Kovacevic-Kuzmanovic, A., Miloradovic, V., Tan, R. S., Bodikova, S., Cervenakova, A., Dvorak, M., Gaspar, L., Herman, O., Hrubon, A., Kokles, M., Krastev, G., Payer, J., Prokop, D., Spisakova, M., Adler, D., Basson, M., Breedt, J., Engelbrecht, J., Jacobson, B., Mitha, I., Van Dyk, C., Alvarez Sala, L. A., Barbagelata Lopez, C., Bisbe, J., Castro Guardiola, A., Cepeda, J. M., Cereto, F., Diaz Santos, E., Ferrer, R., Gomez Cerezo, J., Gonzales-Porras, J. R., Grandes, J., Jimenez, D., Martin Loeches, I., Mellibovsky, L., Richart, C., Riera, A., Trujillo, J., Vargas Nunez, J. A., Villalta, J., Akgul, O., Guneri, S., Kilichesmez, K., Kirma, C., Kutluk, H., Nazliel, B., Okumus, G., Ongen, G., Tigen, K., Topcuoglu, M., Tuncay, E., Abrahamovych, O., Batushkin, V., Brozhyk, J., Burmak, I., Godlevska, O., Goloborodko, A., Goloborodko, B., Goncharova, Y., Gryb, V., Karpenko, O., Kopytsya, M., Koshlia, V., Krakhmalova, O., Kyrychenko, I., Legkonogov, O., Malynovsky, Y., Maslovaskyi, V., Nikonov, V., Parkhomenko, O., Perepeliuk, M., Reshotko, D., Rudenko, L., Ryabichenko, T., Svyridova, I., Svyshchenko, Y., Tseluyko, V., Ursol, G., Vakaliuk, I., Vishnivestsky, I., Voronkov, L., Yagensky, A., Body, R., Chandra, D., Davis, M., Kesteven, P., Maccallum, P., Mccollum, C., Natarajan, I., Almasri, E., Amin, M., Anderson, C., Baker, S., Barney, J., Bastani, B. B. A., Bercz, P., Bidair, M., Carman, T., Chang, H., Clark, C., Concha, M., Cornell, J., Dhingra, R., Doshi, A., Ebrahimi, R., Farley, B., Fermann, G., Foster, G., Fraiz, J., Fulmer, J., Gaggin, H., Goytia-Leos, D., Hahn, B., Haidar, A., Hamad, A., Hazelrigg, M., Ioachimescu, O., Johnson, B., Kabler, H., Kao, C. -K., Kazimir, M., Kouras, F., Kung, M., Lerner, R., Lopez, J., Macchiavelli, A., Mahal, S., Margolis, B., Mclaren, G., Milling, T., Mittal, M., Nadar, V., Ohaju, V., Ortel, T., Overcash, J., Parthiban, K., Pearl, R., Pineda, L., Pratt, R., Pullman, J., Quintana, O., Rajan, R., Rastogi, P., Rees, C., Rodriguez, W., Saba, F., Shammas, N., Sharma, S., Sokol, S., Stoltz, S., Subich, D., Tuck, M., Updegrove, J., Warner, A., Welch, M., Welker, J., Whitman, B., Wichman, T., Yousef, K., Yusen, R., and Zakai, N.
- Subjects
Male ,pulmonary embolism ,Time Factors ,Pyridines ,Intracranial hemorrhage ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,law.invention ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Risk Factors ,Clinical Studies ,Medicine ,030212 general & internal medicine ,Myocardial infarction ,Original Research ,Ischemic stroke ,Hazard ratio ,Absolute risk reduction ,Venous Thromboembolism ,Middle Aged ,Interventional Cardiology ,Pulmonary embolism ,Death ,myocardial infarction ,Treatment Outcome ,Cardiovascular Diseases ,Anesthesia ,Acute Disease ,Benzamides ,Number needed to treat ,Female ,Cardiology and Cardiovascular Medicine ,Intracranial Hemorrhages ,Adult ,venous thromboembolism ,Hemorrhage ,03 medical and health sciences ,Double-Blind Method ,death ,ischemic stroke ,Humans ,Enoxaparin ,Aged ,Proportional Hazards Models ,Inpatients ,Venous thromboembolism ,business.industry ,Settore MED/09 - MEDICINA INTERNA ,Anticoagulants ,Thrombosis ,medicine.disease ,Clinical trial ,chemistry ,Betrixaban ,business ,Acute Coronary Syndromes ,intracranial hemorrhage ,Factor Xa Inhibitors - Abstract
Background Extended‐duration betrixaban showed a significant reduction in venous thromboembolism in the APEX trial (Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study). Given the variable clinical impact of different efficacy and safety events, one approach to assess net clinical outcomes is to include only those events that are either fatal or cause irreversible harm. Methods and Results This was a post hoc analysis of the APEX trial—a multicenter, double‐blind, randomized controlled trial comparing extended‐duration betrixaban versus standard‐of‐care enoxaparin. A composite of all fatal or irreversible safety (fatal bleeding or intracranial hemorrhage) and efficacy events (cardiopulmonary death, myocardial infarction, pulmonary embolism, and ischemic stroke) was evaluated in a time‐to‐first event analysis. In patients with positive D‐dimer results, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.80% versus 3.54%; hazard ratio, 0.73; absolute risk reduction, 1.26%; number needed to treat, 79 [ P =0.033]) and at study end at 77 days (6.27% versus 4.36%; hazard ratio, 0.70; absolute risk reduction, 1.91%; number needed to treat, 52 [ P =0.005]) versus enoxaparin. In all patients, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.08% versus 2.90%; hazard ratio, 0.71; absolute risk reduction, 1.18%; number needed to treat, 86 [ P =0.006]) and 77 days (5.17% versus 3.64%; hazard ratio, 0.70; absolute risk reduction, 1.53%; number needed to treat, 65 [ P =0.002]). Conclusions Among hospitalized medically ill patients, extended‐duration betrixaban demonstrated an ≈30% reduction in fatal or irreversible ischemic or bleeding events compared with standard‐duration enoxaparin. A total of 65 patients would require treatment with betrixaban to prevent 1 fatal or irreversible event versus enoxaparin. Clinical Trial Registration URL : http://www.ClinicalTrials.gov . Unique identifier: NCT 01583218.
- Published
- 2017
15. The safety and efficacy of full- versus reduced-dose betrixaban in the Acute Medically Ill VTE (Venous Thromboembolism) Prevention With Extended-Duration Betrixaban (APEX) trial
- Author
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Raymuno, S., Ramacciotti, E., Manenti, E., Freire, A., Fiss, E., Bizzacchi, J. Annichino, Lienart, F., Dive, A., Delforge, M., Blockmans, D., Soroka, N., Kamenova, Z., Kostadinova, M., Milanova, M., Pencheva, G., Runev, N., Stoeva, N., Stoyanov, M., Syulemzova, S., Todorov, G., Polonetsy, L., Pimanov, S., Mitkovskaya, N., Tokmakova, M., Dhar, A., Mikhailova, E., Koryk, V., Adzerikho, I., Schoenerr, H., Mathies, R., Douketis, J., Konig, J., Le Gal, G., Pearce, M., Provencher, S., Verreault, S., Alarcon, M. Arias, Lazcano, M. Opazo, Cardenas, S. Potthoff, Butkovic-Soldo, S., Car, S., Ciglenecki, N., Francetic, I., Jakopovic, M., Kalinic-Grgorinic, H., Knezevic, A., Marusic, S., Vagic, J. Sikic, Skerk, V., Cermak, O., Gibson, C. Michael, Halaby, Rim, Korjian, Serge, Daaboul, Yazan, Arbetter, Douglas F., Yee, Megan K., Chlumsky, J., Chochola, J., Cizek, V., Goldhaber, Samuel Z., Hull, Russel, Hernandez, Adrian F., Huber, K., Lu, Shiao-ping, Dunaj, M., Dusek, J., Francek, L., Havelka, J., Herold, M., Holaj, R., Nazliel, BİJEN, Bandman, Olga, Leeds, Janet M., Gold, Alex, Harrington, Robert A., Bello, F., Ferrari, A. E., Jure, H., Macin, S., Oliva, M., Parody, M., Horny, I., Hubac, J., Jajtner, P., Kolman, P., Poy, C., Baker, R., Lang, P., Mikulova, J., Podpera, I., Reiterer, P., Spacek, R., Vejvoda, J., Vyhnanek, M., Christensen, H., Lassen, M., Storgaard, M., Tuxen, C., Urhammer, S., Lember, M., Uuetoa, T., Airaksinen, J., Honkaniemi, J., Kaaja, R., Saarinen, J., Tatlisumak, T., Vikman, S., Agraou, B., Aquilanti, S., Belhassane, A., Brisot, D., De Geeter, G., Coughlin, P., Finfer, S., Debourdeau, P., Decoulx, E., El Kouri, D., Falvo, N., Grange, C., Rubinfeld, A., Lacroix, P., Messas, E., Mismetti, P., Montaclair, K., Paleiron, N., Payot, L., Zakai, N., Yousef, K., Wichman, T., Whitman, B., Welker, J., Welch, M., Warner, A., Updegrove, J., Tuck, M., Stoltz, S., Sokol, S., Sharma, S., Shammas, N., Saba, F., Rodriguez, W., Rastogi, P., Rajan, R., Quintana, O., Pullman, J., Pratt, R., Pineda, L., Pernod, G., Pearl, R., Parthiban, K., Ortel, T., Ohaju, V., Pottier, P., Proust, A., Quere, I., Roy, P-M., Schmidt, J., Simoneau, G., Datikashvili-David, I., Khabeishvili, G., Khintibidze, I., Nadar, V., Mittal, M., Milling, T., McLaren, G., Margolis, B., Mahal, S., Macchiavelli, A., Lopez, J., Lerner, R., Kung, M., Kouras, F., Kazimir, M., Kao, C-K., Kabler, H., Ioachimescu, O., Hazelrigg, M., Hamad, A., Haidar, A., Hahn, B., Goytia-Leos, D., Gaggin, H., Fulmer, J., Fraiz, J., Fermann, G., Farley, B., Doshi, A., Dhingra, R., Cornell, J., Concha, M., Clark, C., Chang, H., Carman, T., Bidair, M., Bercz, P., Bastani, A., Barney, J., Baker, S., Anderson, C., Amin, M., Almasri, E., Natarajan, I., McCollum, C., MacCallum, P., Davis, M., Body, R., Yagensky, A., Voronkov, L., Vishnivestsky, I., Vakaliuk, I., Ursol, G., Tseluyko, V., Svyshchenko, Y., Svyridova, I., Ryabichenko, T., Rudenko, L., Reshotko, D., Perepeliuk, M., Parkhomenko, O., Nikonov, V., Maslovaskyi, V., Malynovsky, Y., Legkonogov, O., Kyrychenko, I., Krakhmalova, O., Koshlia, V., Kopytsya, M., Karpenko, O., Gryb, V., Goncharova, Y., Goloborodko, B., Goloborodko, A., Godlevska, O., Burmak, I., Brozhyk, J., Batushkin, V., Abrahamovych, O., Tuncay, E., Topcuoglu, M., Tigen, K., Okumus, G., Kutluk, H., Kirma, C., Kilichesmez, K., Guneri, S., Akgul, O., Villalta, J., Vargas Nunez, J. A., Trujillo, J., Riera, A., Richart, C., Mellibovsky, L., Jimenez, D., Grandes, J., Gonzales-Porras, J. R., Gomez Cerezo, J., Ferrer, R., Diaz Santos, E., Cereto, F., Cepeda, J. M., Castro Guardiola, A., Bisbe, J., Barbagelata Lopez, C., Alvarez Sala, L. A., Van Dyk, C., Mitha, I., Engelbrecht, J., Breedt, J., Basson, M., Adler, D., Spisakova, M., Payer, J., Krastev, G., Kokles, M., Hrubon, A., Herman, O., Dvorak, M., Cervenakova, A., Bodikova, S., Miloradovic, V., Kovacevic-Kuzmanovic, A., Ilic, S., Celic, V., Apostolovic, S., Vishnevskiy, A., Vishneva, E., Solovyov, O., Simanenkov, V., Shvarts, Y., Shpagina, L., Shapovalova, Y., Sergeeva, E., Reshetko, O., Privalova, E., Popov, D., Nilk, R., Nikolaev, K., Mordovin, V., Maslova, N., Martynenko, V., Martynenko, T., Malygin, A., Kostenko, V., Kosmacheva, E., Kobalava, Z., Klein, G., Khachatryan, N., Ershova, O., Dovgalevskiy, Y., Chefranova, Z., Boldueva, S., Bogdanov, E., Belskaya, G., Barbarash, O., Averkov, O., Arkhipov, M., Apartsin, K., Andreev, D., Abashev, A., Vida-Simiti, L., Stanciulescu, G., Stamate, S., Kobulia, B., Megreladze, I., Pagava, Z., Paposhvili, K., Amann, B., Beyer-Westendorf, J., Blessing, E., Bott, M., Dengler, T., Dziewas, R., Genth-Zotz, S., Hamann, F., Horacek, T., Klimpe, S., Kroning, R., Lapp, H., Lawall, H., Licka, M., Rizos, T., Tiefenbacher, C., Weimar, C., Alkonyi, B., Falukozy, J., Futo, L., Katona, A., Kirschner, R., Kristof, P., Lakatos, F., Lupkovics, G., Merkely, B., Andras, C. Nagy, Nemeth, L., Papp, A., Soltesz, P., Sudar, Z., Szabo, G., Szegedi, N., Timar, G., Valco, J., Vertes, A., Efrati, S., Elias, M., Gafter, A., Hayek, T., Hussein, O., Lishner, M., Lugassy, G., Cerveri, I., D'Angelo, A., De Pellegrin, A., Imberti, D., Landolfi, R., Lembo, G., Lodigiani, C., Moia, M., Molteni, M., Mumoli, N., Novo, S., Orlandini, F., Parisi, R., Pizzini, A., Pomero, F., Salvi, A., Schenone, A., Visona, A., Martinova, V., Pontaga, N., Rozitis, V., Stukena, I., Alekniene, B., Basijokiene, V., Butkiene, Z., Griskeviciene, V., Naudziunas, A., Norvaisiene, R., Norviliene, R., Petrauskiene, R., Poskiene, R., Susinskiene, D., Valavicius, A., Castillo Leon, R., Pereyra, R. Cotrina, Karlo, L. Farjardo, Horna, M., Salas, M., Yanez, L. Toche, Fryze, W., Gaciong, Z., Gniot, J., Gorecka, D., Gruenpeter, P., Grzelakowski, P., Jastrzebski, D., Kucharski, L., Mirek-Bryniarska, E., Pulkowski, G., Sobkowicz, B., Sulik, P., Walasek, L., Waldemar, K., Wrzesinski, K., Balogh, Z. E., Bojinca, M., Marin, I., Musetescu, R., Podoleanu, C., Popescu, M., Kalpachki, R., Grigorov, M., Dimov, B., Rocha, A., Goloshchekin, B., Berrouschot, J., Laszlo, Z., Rees, C., Overcash, J., Prokop, D., and Cohen, Alexander T.
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Relative risk reduction ,Male ,Pyridines ,Population ,Hemorrhage ,030204 cardiovascular system & hematology ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pharmacokinetics ,Randomized controlled trial ,Double-Blind Method ,law ,Medicine ,Humans ,030212 general & internal medicine ,Dosing ,Enoxaparin ,education ,Aged ,Aged, 80 and over ,Venous Thrombosis ,education.field_of_study ,business.industry ,Absolute risk reduction ,Anticoagulants ,Venous Thromboembolism ,Hospitalization ,chemistry ,Concomitant ,Betrixaban ,Anesthesia ,Benzamides ,Female ,Cardiology and Cardiovascular Medicine ,business ,Pulmonary Embolism ,Factor Xa Inhibitors - Abstract
The APEX trial assessed the safety and efficacy of extended-duration thromboprophylaxis using betrixaban versus standard dosing of enoxaparin among hospitalized, acutely ill medical patients. The 80-mg betrixaban dose was halved to 40 mg among subjects with severe renal insufficiency and those receiving a concomitant strong P-glycoprotein inhibitor.This analysis assessed the pharmacokinetics, efficacy, and safety of full- (80 mg) and reduced-dose (40 mg) betrixaban relative to enoxaparin in the APEX trial.The median concentration of betrixaban among subjects administered the 80-mg dose was higher than that of the 40-mg dose (19 ng/mL vs 11 ng/mL, P.001). In the primary analysis cohort 1 (d-dimer ≥2× upper limit of normal), the primary efficacy outcome (asymptomatic proximal deep vein thrombosis, symptomatic proximal or distal deep vein thrombosis, symptomatic nonfatal pulmonary embolism, or venous thromboembolism-related death) was significantly reduced among subjects treated with 80 mg of extended-duration betrixaban versus enoxaparin (6.27% [95/1516] vs 8.39% [130/1549], relative risk reduction=0.26 [0.04-0.42], P=.023), and similarly in the entire primary efficacy outcome population (4.87% [122/2506] vs 7.06% [181/2562], relative risk reduction=0.30 [0.13-0.44], P=.001). There was no difference in the primary outcome for subjects treated with 40 mg betrixaban vs enoxaparin across cohorts. In addition, there was no excess of major bleeding associated with either betrixaban dose compared with enoxaparin.The 80-mg betrixaban dose achieves higher plasma concentrations than the 40-mg dose and, in contrast to the 40-mg dose, is associated with improved efficacy across all cohorts relative to standard-dose enoxaparin without an excess risk of major bleeding in the management of medically ill subjects.
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- 2016
16. Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients
- Author
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Engelbrecht, J., Finfer, S., Van Dyk, C., Cohen, Alexander, Grandes, J., Cepeda, J. M., NAZLIEL, BİJEN, Cohen, Alexander T., Efrati, S., Zakai, N., Yousef, K., Wichman, T., Whitman, B., Welker, J., Welch, M., Warner, A., Updegrove, J., Tuck, M., Stoltz, S., Sokol, S., Sharma, S., Shammas, N., Saba, F., Rodriguez, W., Rees, C., Rastogi, P., Rajan, R., Quintana, O., Pullman, J., Pratt, R., Pineda, L., Pearl, R., Parthiban, K., Overcash, J., Ortel, T., Ohaju, V., Nadar, V., Mittal, M., Milling, T., McLaren, G., Margolis, B., Mahal, S., Macchiavelli, A., Lopez, J., Lerner, R., Kung, M., Kouras, F., Kazimir, M., Kao, C-K., Kabler, H., Ioachimescu, O., Hazelrigg, M., Hamad, A., Haidar, A., Hahn, B., Goytia-Leos, D., Gaggin, H., Fulmer, J., Fraiz, J., Fermann, G., Farley, B., Doshi, A., Dhingra, R., Cornell, J., Concha, M., Clark, C., Chang, H., Carman, T., Bidair, M., Bercz, P., Bastani, A., Barney, J., Baker, S., Anderson, C., Amin, M., Almasri, E., Natarajan, I., McCollum, C., MacCallum, P., Davis, M., Body, R., Yagensky, A., Voronkov, L., Vishnivestsky, I., Vakaliuk, I., Ursol, G., Tseluyko, V., Svyshchenko, Y., Svyridova, I., Ryabichenko, T., Rudenko, L., Alekniene, B., Reshotko, D., Perepeliuk, M., Parkhomenko, O., Nikonov, V., Maslovaskyi, V., Malynovsky, Y., Legkonogov, O., Kyrychenko, I., Krakhmalova, O., Koshlia, V., Kopytsya, M., Karpenko, O., Gryb, V., Goncharova, Y., Goloborodko, B., Goloborodko, A., Godlevska, O., Burmak, I., Brozhyk, J., Batushkin, V., Abrahamovych, O., Tuncay, E., Topcuoglu, M., Tigen, K., Okumus, G., Kutluk, H., Kirma, C., Kilichesmez, K., Guneri, S., Akgul, O., Villalta, J., Vargas Nunez, J. A., Trujillo, J., Riera, A., Richart, C., Mellibovsky, L., Jimenez, D., Gonzales-Porras, J. R., Gomez Cerezo, J., Ferrer, R., Diaz Santos, E., Cereto, F., Castro Guardiola, A., Bisbe, J., Barbagelata Lopez, C., Alvarez Sala, L. A., Mitha, I., Breedt, J., Basson, M., Adler, D., Spisakova, M., Prokop, D., Payer, J., Krastev, G., Kokles, M., Hrubon, A., Herman, O., Dvorak, M., Cervenakova, A., Bodikova, S., Miloradovic, V., Kovacevic-Kuzmanovic, A., Ilic, S., Celic, V., Apostolovic, S., Vishnevskiy, A., Vishneva, E., Solovyov, O., Simanenkov, V., Shvarts, Y., Shpagina, L., Shapovalova, Y., Sergeeva, E., Reshetko, O., Privalova, E., Popov, D., Nilk, R., Nikolaev, K., Mordovin, V., Maslova, N., Martynenko, V., Martynenko, T., Malygin, A., Kostenko, V., Kosmacheva, E., Kobalava, Z., Klein, G., Khachatryan, N., Goloshchekin, B., Ershova, O., Dovgalevskiy, Y., Chefranova, Z., Boldueva, S., Bogdanov, E., Belskaya, G., Barbarash, O., Averkov, O., Arkhipov, M., Apartsin, K., Andreev, D., Abashev, A., Vida-Simiti, L., Stanciulescu, G., Stamate, S., Harrington, Robert A., Goldhaber, Samuel Z., Hull, Russell D., Popescu, M., Wiens, Brian L., Gold, Alex, Hernandez, Adrian F., Gibson, C. Michael, Harrington, Robert, Hull, Russell, Goldhaber, Samuel, Hernandez, Adrian, Ceresetto, Jose Manuel, Colquhoun, David, Pilger, Ernst, Polonetsky, Leonid, Podoleanu, C., Musetescu, R., Marin, I., Bojinca, M., Motte, Serge, Saraiva, Jose Francisco, Balogh, Z. E., Wrzesinski, K., Waldemar, K., Walasek, L., Raev, Dimitar, Mincheva, Valentina, Kahn, Susan, Sulik, P., Canon, Claudia Olivares, Malojcic, Branko, Mayer, Otto, Husted, Steen, Marandi, Toomas, Lassila, Riitta, Mottier, Dominique, Shaburishvili, Tamaz, Bauersachs, Rupert, Zeymer, Uwe, Hajko, Erik, Sobkowicz, B., Zeltser, David, Ageno, Walter, Krievins, Dainis, Bagdonas, Alfredas, Osores, Juan Lema, Tomkowski, Witold, Mot, Stefan, Panchenko, Elizaveta, Tan, Ru San, Gaspar, Ludovit, Jacobson, Barry, Monreal, Manuel, Ongen, Gul, Parkhomenko, Alexander, Uprichard, James, Pulkowski, G., Mirek-Bryniarska, E., Kucharski, L., Jastrzebski, D., Yusen, Roger, Grzelakowski, P., Merli, Geno, Gruenpeter, P., Gorecka, D., Gniot, J., Gaciong, Z., Fryze, W., Peacock, Frank, Schellong, Sebastian, Januzzi, James, Piovella, Franco, Cochet, Madeleine, Michalak, Nathan, Stepanchak, Maria, Spielman, Kathryn, Neal, Brandon, Florea, Ana, Chi, Gerald, Szlosek, Donald, Jain, Purva, Popma, Christopher, Korjian, Serge, Daaboul, Yazan, Halaby, Rim, Yanez, L. Toche, Lemor, Alejandro, Zacarkim, Marcelo, Romero, Gonzalo, Hernandez Elenes, Jesus Rosario, Alvarado, Alonso, Susheela, Ammu, Leitao, Meghan, Salas, M., Bandman, Olga, Horna, M., Strumph, Peter, Vinh, Nancy, Visona, A., Kostadinova, M., Vance, Annemarie, Moia, M., Wiens, Brian, Orlandini, F., Parisi, R., Pontaga, N., Smoak, Carey, Storgaard, M., Molteni, M., Castelino, Rennie, Goodman, Shelly, Stukena, I., Leeds, Janet, al-Khalidi, Hussein, Milanova, M., Karlo, L. Farjardo, Leimberger, Jeffrey, Phillips, Thomas, Rizos, T., Pencheva, G., Pomero, F., Francis, Charles, Novo, S., Pereyra, R. Cotrina, Tiefenbacher, C., Buller, Harry, Roberts, Robin, Prins, Martin, Weimar, C., Tuxen, C., Urhammer, S., Lember, M., Runev, N., Uuetoa, T., Spyropoulos, Alex, Carrier, Marc, Alkonyi, B., Lopes, Renato D., Horacek, T., Airaksinen, J., Honkaniemi, J., Pottier, P., Falukozy, J., Kaaja, R., Stoeva, N., Saarinen, J., Stoyanov, M., Pizzini, A., Devor, Adam, Tatlisumak, T., Kolls, Bradley, Dedrick, Joseph, Todd, Jamie, Jones, William Schuyler, Vikman, S., Agraou, B., Futo, L., Castillo Leon, R., Eapen, Zubin, Katona, A., Proust, A., Quere, I., Kirschner, R., Syulemzova, S., Valavicius, A., Todorov, G., Tokmakova, M., Dhar, A., Klimpe, S., Ahmad, Tariq, Brenna, J. Matthew, Douketis, J., Le Gal, G., Pearce, M., Susinskiene, D., Brito, Flavio, Provencher, S., Rozitis, V., Roy, P-M., Kroning, R., Gulack, Brian, Schmidt, J., Meza, James, Parikh, Kishan, Cooper, Lauren, Poskiene, R., Aquilanti, S., Lapp, H., Kristof, P., Lakatos, F., Laszlo, Z., Belhassane, A., Petrauskiene, R., Pagidipati, Neha, Simoneau, G., Verreault, S., Guimaraes, Patricia, Brisot, D., Perkins, Lynn M., De Geeter, G., Debourdeau, P., Alarcon, M. Arias, Lupkovics, G., Norviliene, R., Wilson, Matthew, Merkely, B., Lazcano, M. Opazo, Collier, Jeannie, Andras, C. Nagy, Cardenas, S. Potthoff, Butkovic-Soldo, S., Norvaisiene, R., Decoulx, E., Hayden, Nikieia, El Kouri, D., Car, S., Nemeth, L., Leizorovicz, Alain, Ciglenecki, N., Naudziunas, A., Datikashvili-David, I., Francetic, I., Jakopovic, M., Becker, Francois, Jennings, Lisa, Khabeishvili, G., Bello, F., Ferrari, A. E., Jure, H., Macin, S., Griskeviciene, V., Kalinic-Grgorinic, H., Falvo, N., Khintibidze, I., Grange, C., Kobulia, B., Knezevic, A., Megreladze, I., Marusic, S., Papp, A., Pagava, Z., Lawall, H., Oliva, M., Paposhvili, K., Parody, M., Amann, B., Soltesz, P., Sudar, Z., Butkiene, Z., Szabo, G., Vagic, J. Sikic, Szegedi, N., Poy, C., Timar, G., Skerk, V., Cermak, O., Valco, J., Baker, R., Coughlin, P., Vertes, A., Rubinfeld, A., Elias, M., Berrouschot, J., Gafter, A., Hayek, T., Chlumsky, J., Lacroix, P., Messas, E., Chochola, J., Cizek, V., Basijokiene, V., Hussein, O., Dunaj, M., Dusek, J., Huber, K., Lishner, M., Lugassy, G., Cerveri, I., D'Angelo, A., De Pellegrin, A., Francek, L., Havelka, J., Konig, J., Beyer-Westendorf, J., Herold, M., Holaj, R., Imberti, D., Landolfi, R., Blessing, E., Mathies, R., Schoenerr, H., Adzerikho, I., Koryk, V., Licka, M., Martinova, V., Horny, I., Mikhailova, E., Mitkovskaya, N., Pimanov, S., Polonetsy, L., Soroka, N., Blockmans, D., Delforge, M., Dive, A., Lienart, F., Bizzacchi, J. Annichino, Fiss, E., Mismetti, P., Freire, A., Hubac, J., Jajtner, P., Manenti, E., Ramacciotti, E., Lembo, G., Raymuno, S., Rocha, A., Kolman, P., Lang, P., Bott, M., Dengler, T., Mikulova, J., Dimov, B., Podpera, I., Reiterer, P., Dziewas, R., Montaclair, K., Genth-Zotz, S., Hamann, F., Paleiron, N., Spacek, R., Payot, L., Vejvoda, J., Vyhnanek, M., Christensen, H., Salvi, A., Lodigiani, C., Pernod, G., Grigorov, M., Lassen, M., Mumoli, N., Kalpachki, R., Kamenova, Z., Schenone, A., Guy's and St Thomas' Hospital [London], Stanford Medicine, Stanford University, Brigham and Women's Hospital [Boston], Thrombosis Research Unit, University of Calgary, Portola Pharmaceuticals (Portola), PORTOLA PHARMACEUTICALS, Division of Cardiology, Duke University Medical Center, Duke Clinical Research Institute (DCRI - DURHAM), Duke University [Durham], Beth Israel Deaconess Medical Center [Boston, USA], Harvard Medical School [Boston] (HMS), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)
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Male ,Pyridines ,Medizin ,030204 cardiovascular system & hematology ,law.invention ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,Risk Factors ,law ,030212 general & internal medicine ,ComputingMilieux_MISCELLANEOUS ,Ultrasonography ,Venous Thrombosis ,Factors de risc en les malalties ,Medicine (all) ,Acute Disease ,Adult ,Aged ,Benzamides ,Double-Blind Method ,Drug Administration Schedule ,Factor Xa Inhibitors ,Female ,Fibrin Fibrinogen Degradation Products ,Hemorrhage ,Hospitalization ,Humans ,Middle Aged ,Pulmonary Embolism ,Venous Thromboembolism ,General Medicine ,3. Good health ,Pulmonary embolism ,Venous thrombosis ,Cohort ,medicine.medical_specialty ,Patients ,Risk factors in diseases ,Placebo ,03 medical and health sciences ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Internal medicine ,Thromboembolism ,medicine ,Pacients ,Betrixaban ,Thromboprophylaxis ,Acutely Ill Medical Patients ,Tromboembolisme ,business.industry ,Settore MED/09 - MEDICINA INTERNA ,ta3121 ,Population cohort ,medicine.disease ,Surgery ,chemistry ,Once daily ,business - Abstract
Background\ud Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown.\ud \ud Methods\ud Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding.\ud \ud Results\ud A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55).\ud \ud Conclusions\ud Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.)
- Published
- 2016
- Full Text
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17. Extended thromboprophylaxis with betrixaban in acutely ill medical patients
- Author
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Cohen, A. T., Harrington, R. A., Goldhaber, S. Z., Hull, R. D., Wiens, B. L., Gold, A., Hernandez, A. F., Gibson, C. M., Bello, F., Ferrari, A. E., Jure, H., Macin, S., Oliva, M., Parody, M., Poy, C., Baker, R., Colquhoun, D., Coughlin, P., Finfer, S., Rubinfeld, A., Huber, K., Konig, J., Mathies, R., Pilger, E., Schoenerr, H., Adzerikho, I., Koryk, V., Mikhailova, E., Mitkovskaya, N., Pimanov, S., Polonetsy, L., Soroka, N., Blockmans, D., Delforge, M., Dive, A., Lienart, F., Motte, S., Bizzacchi, J., Fiss, E., Freire, A., Manenti, E., Ramacciotti, E., Raymuno, S., Rocha, A., Saraiva, J. F., Dimov, B., Grigorov, M., Kalpachki, R., Kamenova, Z., Kostadinova, M., Milanova, M., Mincheva, V., Pencheva, G., Raev, D., Runev, N., Stoeva, N., Stoyanov, M., Syulemzova, S., Todorov, G., Tokmakova, M., Dhar, A., Douketis, J., Kahn, S., Le Gal, G., Pearce, M., Provencher, S., Verreault, S., Alarcon, M., Canon, C., Lazcano, M., Cardenas, S., Butkovic-Soldo, S., Car, S., Ciglenecki, N., Francetic, I., Jakopovic, M., Kalinic-Grgorinic, H., Knezevic, A., Malojcic, B., Marusic, S., Vagic, J., Skerk, V., Cermak, O., Chlumsky, J., Chochola, J., Cizek, V., Dunaj, M., Dusek, J., Francek, L., Havelka, J., Herold, M., Holaj, R., Horny, I., Hubac, J., Jajtner, P., Kolman, P., Lang, P., Mayer, O., Mikulova, J., Podpera, I., Reiterer, P., Spacek, R., Vejvoda, J., Vyhnanek, M., Christensen, H., Lassen, M., Storgaard, M., Tuxen, C., Urhammer, S., Lember, M., Marandi, T., Uuetoa, T., Airaksinen, J., Honkaniemi, J., Kaaja, R., Lassila, R., Saarinen, J., Tatlisumak, T., Vikman, S., Agraou, B., Aquilanti, S., Belhassane, A., Brisot, D., De Geeter, G., Debourdeau, P., Decoulx, E., El Kouri, D., Falvo, N., Grange, C., Lacroix, P., Messas, E., Mismetti, P., Montaclair, K., Mottier, D., Paleiron, N., Payot, L., Pernod, G., Pottier, P., Proust, A., Quere, I., Roy, P. M., Schmidt, J., Simoneau, G., Datikashvili-David, I., Khabeishvili, G., Khintibidze, I., Kobulia, B., Megreladze, I., Pagava, Z., Paposhvili, K., Shaburishvili, T., Amann, B., Berrouschot, J., Beyer-Westendorf, J., Blessing, E., Bott, M., Dengler, T., Dziewas, R., Genth-Zotz, S., Hamann, F., Horacek, T., Klimpe, S., Kroning, R., Lapp, H., Lawall, H., Licka, M., Rizos, T., Schellong, S., Tiefenbacher, C., Weimar, C., Zeymer, U., Alkonyi, B., Falukozy, J., Futo, L., Katona, A., Kirschner, R., Kristof, P., Lakatos, F., Laszlo, Z., Lupkovics, G., Merkely, B., Andras, C., Nemeth, L., Papp, A., Soltesz, P., Sudar, Z., Szabo, G., Szegedi, N., Timar, G., Valco, J., Vertes, A., Efrati, S., Elias, M., Gafter, A., Hayek, T., Hussein, O., Lishner, M., Lugassy, G., Zeltser, D., Ageno, W., Cerveri, I., D'Angelo, A., De Pellegrin, A., Imberti, D., Landolfi, Raffaele, Lembo, G., Lodigiani, C., Moia, M., Molteni, M., Mumoli, N., Novo, S., Orlandini, F., Parisi, R., Pizzini, A., Pomero, F., Salvi, A., Schenone, A., Visona, A., Krievins, D., Martinova, V., Pontaga, N., Rozitis, V., Stukena, I., Alekniene, B., Bagdonas, A., Basijokiene, V., Butkiene, Z., Griskeviciene, V., Naudziunas, A., Norvaisiene, R., Norviliene, R., Petrauskiene, R., Poskiene, R., Susinskiene, D., Valavicius, A., Leon, R., Pereyra, R., Karlo, L., Horna, M., Osores, J., Salas, M., Yanez, L., Fryze, W., Gaciong, Z., Gniot, J., Gorecka, D., Gruenpeter, P., Grzelakowski, P., Jastrzebski, D., Kucharski, L., Mirek-Bryniarska, E., Pulkowski, G., Sobkowicz, B., Sulik, P., Tomkowski, W., Walasek, L., Waldemar, K., Wrzesinski, K., Balogh, Z. E., Bojinca, M., Marin, I., Mot, S., Musetescu, R., Podoleanu, C., Popescu, M., Stamate, S., Stanciulescu, G., Vida-Simiti, L., Abashev, A., Andreev, D., Apartsin, K., Arkhipov, M., Averkov, O., Barbarash, O., Belskaya, G., Bogdanov, E., Boldueva, S., Chefranova, Z., Dovgalevskiy, Y., Ershova, O., Goloshchekin, B., Khachatryan, N., Klein, G., Kobalava, Z., Kosmacheva, E., Kostenko, V., Malygin, A., Martynenko, T., Martynenko, V., Maslova, N., Mordovin, V., Nikolaev, K., Nilk, R., Panchenko, E., Popov, D., Privalova, E., Reshetko, O., Sergeeva, E., Shapovalova, Y., Shpagina, L., Shvarts, Y., Simanenkov, V., Solovyov, O., Vishneva, E., Vishnevskiy, A., Apostolovic, S., Celic, V., Ilic, S., Kovacevic-Kuzmanovic, A., Miloradovic, V., Tan, R. S., Bodikova, S., Cervenakova, A., Dvorak, M., Gaspar, L., Herman, O., Hrubon, A., Kokles, M., Krastev, G., Payer, J., Prokop, D., Spisakova, M., Adler, D., Basson, M., Breedt, J., Engelbrecht, J., Jacobson, B., Mitha, I., Van Dyk, C., Sala, L. A., Lopez, C., Bisbe, J., Guardiola, A., Cepeda, J. M., Cereto, F., Santos, E., Ferrer, R., Cerezo, J., Gonzales-Porras, J. R., Grandes, J., Jimenez, D., Mellibovsky, L., Richart, C., Riera, A., Trujillo, J., Nunez, J. A., Villalta, J., Akgul, O., Guneri, S., Kilichesmez, K., Kirma, C., Kutluk, H., Nazliel, B., Okumus, G., Ongen, G., Tigen, K., Topcuoglu, M., Tuncay, E., Abrahamovych, O., Batushkin, V., Brozhyk, J., Burmak, I., Godlevska, O., Goloborodko, A., Goloborodko, B., Goncharova, Y., Gryb, V., Karpenko, O., Kopytsya, M., Koshlia, V., Krakhmalova, O., Kyrychenko, I., Legkonogov, O., Malynovsky, Y., Maslovaskyi, V., Nikonov, V., Parkhomenko, O., Perepeliuk, M., Reshotko, D., Rudenko, L., Ryabichenko, T., Svyridova, I., Svyshchenko, Y., Tseluyko, V., Ursol, G., Vakaliuk, I., Vishnivestsky, I., Voronkov, L., Yagensky, A., Body, R., Davis, M., Maccallum, P., Mccollum, C., Natarajan, I., Almasri, E., Amin, M., Anderson, C., Baker, S., Barney, J., Bastani, A., Bercz, P., Bidair, M., Carman, T., Chang, H., Clark, C., Concha, M., Cornell, J., Dhingra, R., Doshi, A., Farley, B., Fermann, G., Fraiz, J., Fulmer, J., Gaggin, H., Goytia-Leos, D., Hahn, B., Haidar, A., Hamad, A., Hazelrigg, M., Ioachimescu, O., Kabler, H., Kao, C. K., Kazimir, M., Koura, F., Kung, M., Lerner, R., Lopez, J., Macchiavelli, A., Mahal, S., Margolis, B., Mclaren, G., Milling, T., Mittal, M., Nadar, V., Ohaju, V., Ortel, T., Overcash, J., Parthiban, K., Pearl, R., Pineda, L., Pratt, R., Pullman, J., Quintana, O., Rajan, R., Rastogi, P., Rees, C., Rodriguez, W., Saba, F., Shammas, N., Sharma, S., Sokol, S., Stoltz, S., Tuck, M., Updegrove, J., Warner, A., Welch, M., Welker, J., Whitman, B., Wichman, T., Yousef, K., Yusen, R., Zakai, N., Landolfi R. (ORCID:0000-0002-7913-8576), Cohen, A. T., Harrington, R. A., Goldhaber, S. Z., Hull, R. D., Wiens, B. L., Gold, A., Hernandez, A. F., Gibson, C. M., Bello, F., Ferrari, A. E., Jure, H., Macin, S., Oliva, M., Parody, M., Poy, C., Baker, R., Colquhoun, D., Coughlin, P., Finfer, S., Rubinfeld, A., Huber, K., Konig, J., Mathies, R., Pilger, E., Schoenerr, H., Adzerikho, I., Koryk, V., Mikhailova, E., Mitkovskaya, N., Pimanov, S., Polonetsy, L., Soroka, N., Blockmans, D., Delforge, M., Dive, A., Lienart, F., Motte, S., Bizzacchi, J., Fiss, E., Freire, A., Manenti, E., Ramacciotti, E., Raymuno, S., Rocha, A., Saraiva, J. F., Dimov, B., Grigorov, M., Kalpachki, R., Kamenova, Z., Kostadinova, M., Milanova, M., Mincheva, V., Pencheva, G., Raev, D., Runev, N., Stoeva, N., Stoyanov, M., Syulemzova, S., Todorov, G., Tokmakova, M., Dhar, A., Douketis, J., Kahn, S., Le Gal, G., Pearce, M., Provencher, S., Verreault, S., Alarcon, M., Canon, C., Lazcano, M., Cardenas, S., Butkovic-Soldo, S., Car, S., Ciglenecki, N., Francetic, I., Jakopovic, M., Kalinic-Grgorinic, H., Knezevic, A., Malojcic, B., Marusic, S., Vagic, J., Skerk, V., Cermak, O., Chlumsky, J., Chochola, J., Cizek, V., Dunaj, M., Dusek, J., Francek, L., Havelka, J., Herold, M., Holaj, R., Horny, I., Hubac, J., Jajtner, P., Kolman, P., Lang, P., Mayer, O., Mikulova, J., Podpera, I., Reiterer, P., Spacek, R., Vejvoda, J., Vyhnanek, M., Christensen, H., Lassen, M., Storgaard, M., Tuxen, C., Urhammer, S., Lember, M., Marandi, T., Uuetoa, T., Airaksinen, J., Honkaniemi, J., Kaaja, R., Lassila, R., Saarinen, J., Tatlisumak, T., Vikman, S., Agraou, B., Aquilanti, S., Belhassane, A., Brisot, D., De Geeter, G., Debourdeau, P., Decoulx, E., El Kouri, D., Falvo, N., Grange, C., Lacroix, P., Messas, E., Mismetti, P., Montaclair, K., Mottier, D., Paleiron, N., Payot, L., Pernod, G., Pottier, P., Proust, A., Quere, I., Roy, P. M., Schmidt, J., Simoneau, G., Datikashvili-David, I., Khabeishvili, G., Khintibidze, I., Kobulia, B., Megreladze, I., Pagava, Z., Paposhvili, K., Shaburishvili, T., Amann, B., Berrouschot, J., Beyer-Westendorf, J., Blessing, E., Bott, M., Dengler, T., Dziewas, R., Genth-Zotz, S., Hamann, F., Horacek, T., Klimpe, S., Kroning, R., Lapp, H., Lawall, H., Licka, M., Rizos, T., Schellong, S., Tiefenbacher, C., Weimar, C., Zeymer, U., Alkonyi, B., Falukozy, J., Futo, L., Katona, A., Kirschner, R., Kristof, P., Lakatos, F., Laszlo, Z., Lupkovics, G., Merkely, B., Andras, C., Nemeth, L., Papp, A., Soltesz, P., Sudar, Z., Szabo, G., Szegedi, N., Timar, G., Valco, J., Vertes, A., Efrati, S., Elias, M., Gafter, A., Hayek, T., Hussein, O., Lishner, M., Lugassy, G., Zeltser, D., Ageno, W., Cerveri, I., D'Angelo, A., De Pellegrin, A., Imberti, D., Landolfi, Raffaele, Lembo, G., Lodigiani, C., Moia, M., Molteni, M., Mumoli, N., Novo, S., Orlandini, F., Parisi, R., Pizzini, A., Pomero, F., Salvi, A., Schenone, A., Visona, A., Krievins, D., Martinova, V., Pontaga, N., Rozitis, V., Stukena, I., Alekniene, B., Bagdonas, A., Basijokiene, V., Butkiene, Z., Griskeviciene, V., Naudziunas, A., Norvaisiene, R., Norviliene, R., Petrauskiene, R., Poskiene, R., Susinskiene, D., Valavicius, A., Leon, R., Pereyra, R., Karlo, L., Horna, M., Osores, J., Salas, M., Yanez, L., Fryze, W., Gaciong, Z., Gniot, J., Gorecka, D., Gruenpeter, P., Grzelakowski, P., Jastrzebski, D., Kucharski, L., Mirek-Bryniarska, E., Pulkowski, G., Sobkowicz, B., Sulik, P., Tomkowski, W., Walasek, L., Waldemar, K., Wrzesinski, K., Balogh, Z. E., Bojinca, M., Marin, I., Mot, S., Musetescu, R., Podoleanu, C., Popescu, M., Stamate, S., Stanciulescu, G., Vida-Simiti, L., Abashev, A., Andreev, D., Apartsin, K., Arkhipov, M., Averkov, O., Barbarash, O., Belskaya, G., Bogdanov, E., Boldueva, S., Chefranova, Z., Dovgalevskiy, Y., Ershova, O., Goloshchekin, B., Khachatryan, N., Klein, G., Kobalava, Z., Kosmacheva, E., Kostenko, V., Malygin, A., Martynenko, T., Martynenko, V., Maslova, N., Mordovin, V., Nikolaev, K., Nilk, R., Panchenko, E., Popov, D., Privalova, E., Reshetko, O., Sergeeva, E., Shapovalova, Y., Shpagina, L., Shvarts, Y., Simanenkov, V., Solovyov, O., Vishneva, E., Vishnevskiy, A., Apostolovic, S., Celic, V., Ilic, S., Kovacevic-Kuzmanovic, A., Miloradovic, V., Tan, R. S., Bodikova, S., Cervenakova, A., Dvorak, M., Gaspar, L., Herman, O., Hrubon, A., Kokles, M., Krastev, G., Payer, J., Prokop, D., Spisakova, M., Adler, D., Basson, M., Breedt, J., Engelbrecht, J., Jacobson, B., Mitha, I., Van Dyk, C., Sala, L. A., Lopez, C., Bisbe, J., Guardiola, A., Cepeda, J. M., Cereto, F., Santos, E., Ferrer, R., Cerezo, J., Gonzales-Porras, J. R., Grandes, J., Jimenez, D., Mellibovsky, L., Richart, C., Riera, A., Trujillo, J., Nunez, J. A., Villalta, J., Akgul, O., Guneri, S., Kilichesmez, K., Kirma, C., Kutluk, H., Nazliel, B., Okumus, G., Ongen, G., Tigen, K., Topcuoglu, M., Tuncay, E., Abrahamovych, O., Batushkin, V., Brozhyk, J., Burmak, I., Godlevska, O., Goloborodko, A., Goloborodko, B., Goncharova, Y., Gryb, V., Karpenko, O., Kopytsya, M., Koshlia, V., Krakhmalova, O., Kyrychenko, I., Legkonogov, O., Malynovsky, Y., Maslovaskyi, V., Nikonov, V., Parkhomenko, O., Perepeliuk, M., Reshotko, D., Rudenko, L., Ryabichenko, T., Svyridova, I., Svyshchenko, Y., Tseluyko, V., Ursol, G., Vakaliuk, I., Vishnivestsky, I., Voronkov, L., Yagensky, A., Body, R., Davis, M., Maccallum, P., Mccollum, C., Natarajan, I., Almasri, E., Amin, M., Anderson, C., Baker, S., Barney, J., Bastani, A., Bercz, P., Bidair, M., Carman, T., Chang, H., Clark, C., Concha, M., Cornell, J., Dhingra, R., Doshi, A., Farley, B., Fermann, G., Fraiz, J., Fulmer, J., Gaggin, H., Goytia-Leos, D., Hahn, B., Haidar, A., Hamad, A., Hazelrigg, M., Ioachimescu, O., Kabler, H., Kao, C. K., Kazimir, M., Koura, F., Kung, M., Lerner, R., Lopez, J., Macchiavelli, A., Mahal, S., Margolis, B., Mclaren, G., Milling, T., Mittal, M., Nadar, V., Ohaju, V., Ortel, T., Overcash, J., Parthiban, K., Pearl, R., Pineda, L., Pratt, R., Pullman, J., Quintana, O., Rajan, R., Rastogi, P., Rees, C., Rodriguez, W., Saba, F., Shammas, N., Sharma, S., Sokol, S., Stoltz, S., Tuck, M., Updegrove, J., Warner, A., Welch, M., Welker, J., Whitman, B., Wichman, T., Yousef, K., Yusen, R., Zakai, N., and Landolfi R. (ORCID:0000-0002-7913-8576)
- Abstract
BACKGROUND: Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. METHODS: Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated D-dimer level (cohort 1), patients with an elevated D-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. RESULTS: A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P = 0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P = 0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P = 0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P = 0.55). CONCLUSIONS: Among acutely ill medical patients with an elevated D-dimer level, there was no
- Published
- 2016
18. Oral Apixaban for the Treatment of Acute Venous Thromboembolism
- Author
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Agnelli, G, Buller, H, Cohen, A, Gallus, A, Raskob, G, Weitz, J, Prins, M, Brandjes, D, Kolbach, D, Limburg, M, Mac Gillavry, M, Otten, Jm, Peters, R, Roos, Y, Segers, A, Slagboom, T, Bounameaux, H, Hirsh, J, Samama, Mm, Wedel, H, Curto, M, Johnson, M, Masiukiewicz, U, Pak, R, Porcari, A, Sanders, P, Sisson, M, Sullivan, B, Thompson, J, Auerbach, J, Cesario, L, Crawford, J, Gordon, M, Noble, M, Pennington, A, Reinhold, P, Simmons, M, Urwin, K, Ceresetto, J, Mcrae, S, Pabinger, I, Pereira, Ah, Spencer, F, Wang, C, Zhang, J, Gorican, K, Husted, Se, Mottier, D, Harenberg, J, Vértes, A, Pinjala, R, Zeltser, D, Prandoni, Paolo, Sandset, M, Torbicki, A, Fijalkowska, A, Alvares, Jp, Kirienko, A, Shvarts, Y, Sala, La, Jacobson, B, Gudz, I, Ortel, T, Spyropoulos, A, Beyer Westendorf, J, Sipos, G, Bredikhin, R, Della Siega, A, Klinke, W, Lawall, H, Zwettler, U, Prasol, V, Cannon, K, Vasylyuk, S, Jin, B, Prandoni, P, Desai, S, Zaichuk, A, Katelnitskiy, I, De Pellegrin, A, Santonastaso, M, Skupyy, O, Pesant, Y, Shvalb, P, Spacek, R, Visonà, A, Alvarez Sala, L, Borja, V, Noori, E, Sereg, M, Braester, A, Falvo, N, Vöhringer, H, Laperna, L, Oliven, A, Skalicka, L, Bolster, D, Haidar, A, Schellong, S, Smith, S, Sergeev, O, Pullman, J, Torp Pedersen, C, Zimlichman, R, Elias, M, Fourie, N, Pernod, G, Panchenko, E, Pendleton, R, van Nieuwenhuizen, E, Vinereanu, D, Becattini, C, Manina, G, Leduc, J, Dunaj, M, Frost, L, Gavish, D, Jakobsen, T, Lishner, M, Morales, L, Chochola, J, Gubka, O, Holaj, R, Hussein, O, Katona, A, Sergeeva, E, Bova, C, Cepeda, J, Cohen, K, Sobkowicz, B, Grzelakowski, P, Husted, S, Lupkovics, G, Dedek, V, Liu, C, Puskas, A, Ritchie, B, Ambrosio, G, Parisi, R, Heuer, H, Livneh, A, Podpera, I, Stanbro, M, Caraco, Y, Fulmer, J, Ghirarduzzi, A, Schmidt Lucke, J, Bergmann, J, Cizek, V, Leyden, M, Stein, R, Abramov, I, Chong, B, Colan, D, Jindal, R, Liu, S, Pereira, A, Porreca, E, Salem, H, Welker, J, Yusen, R, Dhar, A, Podczeck Schweighofer, A, Shtutin, O, Vital Durand, D, Balaji, V, Correa, J, Kline, J, Runyon, M, Laszlo, Z, Martelet, M, Parakh, R, Sandset, Pm, Schmidt, J, Yeo, E, Bhagavan, N, Bura Riviere, A, Ferrer, J, Lacroix, P, Lewczuk, J, Pilger, E, Sokurenko, G, Yu, H, Nikulnikov, P, Pabinger Fasching, I, Sanchez Diaz, C, Schuller, D, Suresh, K, Lobo, S, Lyons, R, Marschang, P, Palla, A, Schulman, S, Spyropoulous, A, Fraiz, J, Gerasymov, V, Lerner, R, Llamas Esperón, G, Manenti, E, Masson, J, Moreira, R, Poy, C, Rodoman, G, Bruckner, I, Gurghean, A, Carrier, M, Freire, A, Gan, E, Gibson, K, Herold, M, Hudcovic, M, Kamath, G, Koslow, A, Meneveau, N, Roos, J, Zahn, R, Balanda, J, Bratsch, H, Dolan, S, Gould, T, Hirschl, M, Hoffmann, U, Kaatz, S, Shah, V, Kadapatti, K, Kræmmer Nielsen, H, Lahav, M, Natarajan, S, Tuxen, C, Tveit, A, Alves, C, Formiga, A, Brudevold, R, Cardozo, M, Lorch, D, Marais, H, Mismetti, P, Panico, M, Pop, C, Quist Paulsen, P, Stevens, D, Tarleton, G, Yoshida, W, Cox, M, Crispin, P, Czekalski, P, Ebrahim, I, Game, M, Ghanima, W, Harrington, D, Jackson, D, Lee, A, Matoska, P, Meade, A, Camargo, Ac, Nishinari, K, Sanchez Llamas, F, Tosetto, A, Vejby Christensen, H, Basson, M, Blombery, P, Fu, G, Jha, V, Keltai, K, Le Jeunne, C, Lodigiani, C, Ma, Y, Nagy, A, Neumeister, A, Shotan, A, Wong, T, Ying, K, Anderson, S, Brenner, B, Carnovali, M, Cerana, S, Cunha, C, Diaz Castañon, J, Graham, M, Kirenko, A, Palareti, G, Rodriguez Cintron, W, Nathanson, A, Rosenthal, S, Sanders, D, Scheinberg, P, Schjesvold, F, Torp, R, van Zyl, L, Venher, I, Xia, G, Brockmyre, A, Chen, Z, Hakki, S, Hanefield, C, Mügge, A, Janczak, D, Karpovych, D, Lancaster, G, Lavigne, C, Lugassy, G, Melaniuk, M, Moran, J, Oliver, M, Schattner, A, Staroverov, I, Timi, J, Vöhringer, F, von Bilderling, P, Warr, T, White, R, Wronski, J, Wu, C, Almeida, C, Blum, A, Bono, J, Durán, M, Erzinger, F, Fu, W, Jagadesan, R, Jurecka, W, Korban, E, Nguyen, D, Raval, M, Willms, D, Zevin, S, Zhu, H, Abdullah, I, Achkar, A, Albuquerque, L, Ali, M, Bai, C, Bloomfield, D, Chen, J, Fajardo Campos, P, Garcia Bragado, F, Kobza, I, Lindhoff Last, E, Lourenço, A, Marchena Yglesias, P, Marshall, P, Siegel, M, Mikhailova, O, Oliva, M, Pottier, P, Pruszczyk, P, Sauer, M, Baloira, A, Cromer, M, D'Angelo, A, Faucher, J, Gutowski, P, Hong, S, Lissauer, M, Lopes, A, Lopes, R, Maholtz, M, Mesquita, E, Miekus, P, Mohan, B, Ng, H, Peterson, M, Piovella, F, Siragusa, S, Srinivas, R, Tiberio, G, Van Bellen, B, Arutyunov, G, Assi, N, Baker, R, Blanc, F, Curnow, J, Fu, C, Gonzalez Porras, J, Guijarro Merino, R, Gunasingam, S, Gupta, P, Laule, M, Liu, Z, Luber, J, Serifilippi, G, Paulson, R, Shevela, A, Simonneau, G, Siu, D, Sosa Liprandi, M, Takács, J, Tay, J, Vora, K, Witkiewicz, W, Zhao, L, Aquilanti, S, Dabbagh, O, Dellas, C, Denaro, C, Doshi, A, Flippo, G, Giumelli, C, Gomez Cerezo, J, Han, D, Harris, L, Hofmann L., Jr, Kamerkar, D, Kaminski, L, Kazimir, M, Kloczko, J, Ko, Y, Koura, F, Lavender, R, Maly, J, Margolis, B, Mos, L, Sanchez Escalante, L, Solvang, A, Soroka, V, Szopinski, P, Thawani, H, Vickars, L, Yip, G, Zangroniz, P., Internal and Cardiovascular Medicine - Stroke Unit (PERUGIA - ICM-SU), Università degli Studi di Perugia (UNIPG), Department of Vascular Medicine (DVM - AMC), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), King's College Hospital (KCH), Department of Haematology (ADELAIDE - Dep Haemato), Flinders Medical Centre-Flinders University, Health Sciences Center (OKLAHOMA - HSC), University of Oklahoma (OU), Thrombosis and Atherosclerosis Research Institute (TARI), McMaster University [Hamilton, Ontario], Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, APH - Amsterdam Public Health, Cardiology, ANS - Amsterdam Neuroscience, Neurology, and Other departments
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Male ,MESH: Factor Xa ,[SDV]Life Sciences [q-bio] ,Administration, Oral ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,THERAPY ,MESH: Venous Thromboembolism ,chemistry.chemical_compound ,0302 clinical medicine ,Edoxaban ,MESH: Double-Blind Method ,030212 general & internal medicine ,MESH: Warfarin ,MESH: Treatment Outcome ,MESH: Aged ,RISK ,MESH: Middle Aged ,General Medicine ,MESH: Follow-Up Studies ,Venous Thromboembolism ,Middle Aged ,3. Good health ,Pulmonary embolism ,Treatment Outcome ,MESH: Administration, Oral ,Acute Disease ,MESH: Acute Disease ,Apixaban ,Female ,MESH: Hemorrhage ,medicine.drug ,Andexanet alfa ,Adult ,medicine.medical_specialty ,MESH: Enoxaparin ,Pyridones ,PULMONARY-EMBOLISM ,Hemorrhage ,MESH: Anticoagulants ,03 medical and health sciences ,Double-Blind Method ,BINOMIAL TRIALS ,Internal medicine ,MESH: Pyridones ,medicine ,Humans ,Enoxaparin ,MESH: Kaplan-Meier Estimate ,RIVAROXABAN ,Aged ,Rivaroxaban ,MESH: Humans ,business.industry ,Warfarin ,Anticoagulants ,MESH: Adult ,medicine.disease ,Confidence interval ,MESH: Male ,Surgery ,chemistry ,Relative risk ,Pyrazoles ,business ,MESH: Female ,MESH: Pyrazoles ,Factor Xa Inhibitors ,Follow-Up Studies - Abstract
International audience; BACKGROUND: Apixaban, an oral factor Xa inhibitor administered in fixed doses, may simplify the treatment of venous thromboembolism. METHODS: In this randomized, double-blind study, we compared apixaban (at a dose of 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months) with conventional therapy (subcutaneous enoxaparin, followed by warfarin) in 5395 patients with acute venous thromboembolism. The primary efficacy outcome was recurrent symptomatic venous thromboembolism or death related to venous thromboembolism. The principal safety outcomes were major bleeding alone and major bleeding plus clinically relevant nonmajor bleeding. RESULTS: The primary efficacy outcome occurred in 59 of 2609 patients (2.3%) in the apixaban group, as compared with 71 of 2635 (2.7%) in the conventional-therapy group (relative risk, 0.84; 95% confidence interval [CI], 0.60 to 1.18; difference in risk [apixaban minus conventional therapy], -0.4 percentage points; 95% CI, -1.3 to 0.4). Apixaban was noninferior to conventional therapy (P
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- 2013
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19. Apixaban for extended treatment of venous thromboembolism
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Agnelli, G, Buller, H, Cohen, A, Gallus, A, Raskob, G, Weitz, J, Prins, M, Brandjes, D, Kolbach, D, Limburg, M, Mac Gillavry, M, Otten, Jm, Peters, R, Roos, Y, Segers, A, Slagboom, T, Bounameaux, H, Hirsh, J, Samama, Mm, Wedel, H, Curto, M, Johnson, M, Masiukiewicz, U, Pak, R, Porcari, A, Sanders, P, Sisson, M, Sullivan, B, Thompson, J, Auerbach, J, Cesario, L, Gamero, M, Gordon, M, Griffiths, A, Noble, M, Ott, J, Pennington, A, Peffer, A, Reinhold, P, Simmons, M, Urwin, K, Ceresetto, J, Mcrae, S, Pabinger, I, Pereira, Ah, Spencer, F, Gorican, K, Husted, Se, Mottier, D, Harenberg, J, Pinjala, R, Zeltser, D, Imberti, D, Sandset, M, Torbicki, A, Fijalkowska, A, Albino, Jp, Kirienko, A, Shvarts, Y, Monreal, M, Jacobson, B, Dolan, G, Gudz, I, Ortel, T, Spyropoulos, A, Skupyy, O, Beryer Westendorf, J, De Pellegrin, A, Prasol, V, Schellong, S, Falvo, N, Abramov, I, Cizek, V, Husted, S, Desai, S, Barillari, G, Sergeev, O, Chetter, I, Inbal, A, Mccollum, C, Shvalb, P, Torp Pedersen, C, Vasylyuk, S, Kraemmer Nielsen, H, Pernod, G, Schmidt, J, Bova, C, Gerasymov, V, Pabinger Fasching, I, Skalicka, L, Zaichuk, A, Achkar, A, Bremmelgaard, A, Chochola, J, Gould, T, Khalafallah, A, Jakobsen, T, Rose, P, Zhukov, B, Dedek, V, Mirete Ferrer, J, Pesant, Y, Repin, A, Salem, H, Solis Morales, L, Spacek, R, Cannon, K, Grzelakowski, P, Jindal, R, Pereira, A, Zidkova, E, Ambrosio, G, Cardozo, M, Dunaj, M, Gavish, D, Ghanima, W, Leduc, Jj, Mismetti, P, Panico, M, Porreca, E, Riera, A, Bareford, D, Chong, B, Dvoryashina, I, Gómez Cerezo, J, Kobza, I, Nielsen, T, Pendleton, R, Pullman, J, Schiffman, G, Stanbro, M, Zwettler, U, Aquilanti, S, Bratsch, H, Cohen, K, Elias, D, Gan, E, Holaj, R, Klinke, W, Liu, Hs, Sandset, Pm, van Nieuwenhuizen, E, Álvarez Sala LA, Basson, M, Braester, A, Bura Riviere, A, Calvo Vargas, C, Correa, J, Elias, M, Frost, L, Landolfi, R, Marschang, P, Moreira, R, Natarajan, S, Pottier, P, Tosetto, A, Tuxen, C, Vöhringer, Hf, Alexander, A, Barbarash, O, Fajardo Campos, P, Graham, M, Gubka, O, Hudcovic, M, Hussein, O, Jackson, D, Katelnitskiy, I, Lawall, H, Palareti, G, Poggio, R, Roos, J, Simonneau, G, Smith, Sw, Szopinski, P, Zimlichman, R, Bridgers, D, Colan, D, Czekalski, P, De Jong, D, Fortinez, Jt, Garcia Bragado, F, Harrington, D, Izbicki, G, Kadr, H, Koslow, A, Loftus, I, Marais, H, Neumeister, A, Oliven, A, Palla, A, Pop, C, Prandoni, Paolo, Puskas, A, Sanchez Llamas, F, Shotan, A, Singh, P, Tveit, A, Baker, R, Borja, V, Brenner, B, Brown, H, Cha, Tj, Cohen, Y, D'Angelo, A, Dhar, A, Friis, E, Hueur, H, Jiménez Rodríguez Madridejos, R, Karl, J, Karrasch, J, Lishner, M, Manenti, E, Meneveau, N, Nguyen, D, Sanchez Escalante, L, Santoscoy Ibarra, J, Sokurenko, G, Staroverov, I, Stein, R, Abdullah, I, Alcocer Gamba, M, Balanda, J, Bruckner, I, Calabuig Alborch, J, Caraco, Y, Comerota, A, Cromer, M, de Araujo Filho, J, De los Rios Ibarra, M, Diaz Castañon, J, Doshi, A, Ebrahim, I, Fessel, Wj, Fletcher, E, Fourie, N, Fu, C, Gutowski, P, Haddad, G, Hoffman, U, Jardula, M, Kvasnicka, T, Lewczuk, J, Leyden, M, Livneh, A, Lodigiani, C, Lovell, C, Miekus, P, Paloma, Mj, Parakh, R, Raval, M, Schmidt Lucke, J, Shtutin, O, Soroka, V, Stevens, D, Sulik, P, Tay, Jc, Vejby Christensen, H, Vinereanu, D, Baghestanian, M, Bono, J, Cerana, S, Freire, A, Gibson, K, Giumelli, C, Iastrebner, C, Karpenko, A, Kelly, A, Lacroix, P, Lafata, J, Lobo, S, Macik, Bg, Marchena Yglesias, P, Nishinari, K, Podczeck Schweighofer, A, Raby, K, Sirpal, S, Solymoss, S, van Zyl, L, Vargas Núñez JA, von Bilderling, P, Warr, T, Wronski, J, Wurster, M, Albino, Ja, Albuquerque, L, Averill, F, Baek, Sh, Bello, F, Bergoeing, M, Blanc, Fx, Bloomberg, R, Bolster, D, Brockmyre, A, Calimano, C, Checketts, D, Cieplinski, W, Chervu, A, Collado, F, Denaro, C, Gaciong, Z, Game, M, Iskander, A, Kaatz, S, Kim, Di, Koura, F, Laguna, F, Lanas Zanetti, F, Lindhoff Last, E, Melaniuk, M, Meade, A, Murphy, T, Ng, Hj, Páramo Fernández JA, Patil, C, Piovella, F, Prisco, D, Pruszczyk, P, Reimers, G, Rivera, E, Rodriguez Cintron, W, Rosenthal, S, Salbach, P, Salvador, D, Schuller, D, Siragusa, S, Staniszewski, R, Torp, R, Vora, K, Yip, G, Alfieri, A, Belaji, V, Bhagavan, N, Carnovali, M, Cobos Segarra, J, Di Todaro, F, Dowell, A, Corder, C, Crispin, P, Cuadrado, J, Flippo, G, Fraiz, J, Guillaumon, A, Gvora, T, Hakki, S, Harris, L, Ison, R, Htun, Pt, Jasani, R, Kates, M, Kaminski, L, Kamerkar, D, Kroger, K, Laperna, L, Leiva, J, Luber, J, Mccann, A, Mckenzie, W, Menna Barreto, S, Moran, J, Nikulnikov, P, Paliwal, Y, Patel, M, Pilger, E, Renwick, W, Shevela, A, Starosiliz, D, Stringam, S, To, R, Updegrove, J, Van Bellen, B, Waintrub, M, White, J, Yeo, E, Zangroniz, P, Zeltser, D., ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, APH - Amsterdam Public Health, Cardiology, ANS - Amsterdam Neuroscience, Neurology, Department of Vascular Medicine (DVM - AMC), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Thrombosis and Atherosclerosis Research Institute (TARI), McMaster University [Hamilton, Ontario], Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)
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Male ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,Placebo group ,DISEASE ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,Recurrence ,Fibrinolytic agents ,030212 general & internal medicine ,IDRAPARINUX ,Administration of drugs ,Follow up studies ,food and beverages ,General Medicine ,Venous Thromboembolism ,Middle Aged ,3. Good health ,Intention to Treat Analysis ,Treatment Outcome ,Treatment dose ,Anesthesia ,Creatinine ,Factor Xa ,Fibrinolítics ,Apixaban ,Female ,Administració de medicaments ,Major bleeding ,medicine.drug ,ARTERIAL CARDIOVASCULAR EVENTS ,INTENSITY WARFARIN THERAPY ,PULMONARY-EMBOLISM ,LONG-TERM ,PREVENTION ,Adult ,Pyridones ,Hemorrhage ,03 medical and health sciences ,Double-Blind Method ,Fibrinolytic Agents ,Thromboembolism ,medicine ,Humans ,Tromboembolisme ,Aged ,Intention-to-treat analysis ,business.industry ,fungi ,Pyrazoles ,business ,Venous thromboembolism ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Factor Xa Inhibitors ,Follow-Up Studies - Abstract
International audience; Background Apixaban, an oral factor Xa inhibitor that can be administered in a simple, fixed-dose regimen, may be an option for the extended treatment of venous thromboembolism. Methods In this randomized, double-blind study, we compared two doses of apixaban (2.5 mg and 5 mg, twice daily) with placebo in patients with venous thromboembolism who had completed 6 to 12 months of anticoagulation therapy and for whom there was clinical equipoise regarding the continuation or cessation of anticoagulation therapy. The study drugs were administered for 12 months. Results A total of 2486 patients underwent randomization, of whom 2482 were included in the intention-to-treat analyses. Symptomatic recurrent venous thromboembolism or death from venous thromboembolism occurred in 73 of the 829 patients (8.8%) who were receiving placebo, as compared with 14 of the 840 patients (1.7%) who were receiving 2.5 mg of apixaban (a difference of 7.2 percentage points; 95% confidence interval [CI], 5.0 to 9.3) and 14 of the 813 patients (1.7%) who were receiving 5 mg of apixaban (a difference of 7.0 percentage points; 95% CI, 4.9 to 9.1) (P
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- 2012
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20. Competitive Spreading versus Imbibition of Polymer Liquid Drops in Nanoporous Membranes: Scaling Behavior with Viscosity.
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H. Haidara, B. Lebeau, C. Grzelakowski, L. Vonna, F. Biguenet, and L. Vidal
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- 2008
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21. Amphiphilic Copolymer Membranes Promote NADH:Ubiquinone Oxidoreductase Activity: Towards an ElectronTransfer Nanodevice
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Graff, Alexandra, FraysseAilhas, Caroline, Palivan, Cornelia G., Grzelakowski, Mariusz, Friedrich, Thorsten, Vebert, Corinne, Gescheidt, Georg, and Meier, Wolfgang
- Abstract
Nanoscale devices for energy conversion require the transfer of electrons from one compartment to another. The enzyme complex I, which in vivo mediates electron transfer from NADH to ubiquinone, is an intriguing candidate for this role in nanodevices. However, complex I normally requires the presence of lipids to remain active, potentially limiting its application. Here we demonstrate for the first time that complex I can be actively reconstituted in the synthetic membrane of amphiphilic triblock copolymer vesicles. The functionality of the reconstituted protein was characterized by EPR and activity assays. Its activity is strongly influenced by the molar mass and the block length of the membraneforming polymers, and increases with increasing membrane thickness.
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- 2010
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22. Inhibition of Macrophage Phagocytotic Activity by a Receptor-targeted Polymer Vesicle-based Drug Delivery Formulation of Pravastatin
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Broz, Pavel, Ben-Haim, Nadav, Grzelakowski, Mariusz, Marsch, Stephan, Meier, Wolfgang, and Hunziker, Patrick
- Abstract
Ruptures of macrophage-rich atherosclerotic plaques in the coronary arteries are the main reason for heart attack. Targeted therapeutic interventions with an inhibitory effect on the macrophages promise to be beneficial, but currently available drugs such as statins achieve event reductions of only 30%. Dose-limiting adverse effects in remote organs prohibit achieving higher drug levels known to have strong inhibitory effects on macrophages. Receptor-specific targeting using statin-loaded nanometer-sized triblock copolymer vesicles with targeting moieties might allow high-dose treatment for improved efficacy, while minimizing toxicity in other cells. Vesicle uptake by target cells but not other cell types and slow intracellular content release was observed. A major improvement in biologic efficacy was observed for polymer vesicles compared to free drug, whereas no increased cytotoxicity was observed in muscle cells. Such high-dose, targeted therapy of statins through cell-specific polymer vesicles allows novel treatment paradigms not only for atherosclerosis, but appears promising for a wide range of drugs and diseases.
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- 2008
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23. Fast elemental mapping and magnetic imaging with high lateral resolution using a novel photoemission microscope
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Ziethen, C., Schmidt, O., Fecher, G. H., Schneider, C. M., Schoenhense, G., Froemter, R., Seider, M., Grzelakowski, K., Merkel, M., and Funnemann, D.
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- 1998
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24. Recent progress in photoemission microscopy with emphasis on chemical and magnetic sensitivity
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Swiech, W., Fecher, G. H., Ziethen, C., Schmidt, O., Schoenhense, G., Grzelakowski, K., Schneider, C. M., Froemter, R., Oepen, H. P., and Kirschner, J.
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- 1997
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25. Functionalized Nanocompartments (Synthosomes) with a Reduction-Triggered Release System
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Onaca, Ozana, Sarkar, Pransenjit, Roccatano, Danilo, Friedrich, Thomas, Hauer, Bernard, Grzelakowski, Mariusz, Güven, Arcan, Fioroni, Marco, and Schwaneberg, Ulrich
- Abstract
No Abstract
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- 2008
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26. Multi-technique application of a double reflection electron emission microscope
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Grzelakowski, K
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- 2000
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27. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism
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Weitz, Jeffrey I., Lensing, Anthonie W.A., Prins, Martin H., Bauersachs, Rupert, Beyer-Westendorf, Jan, Bounameaux, Henri, Brighton, Timothy A., Cohen, Alexander T., Davidson, Bruce L., Decousus, Hervé, Freitas, Maria C.S., Holberg, Gerlind, Kakkar, Ajay K., Haskell, Lloyd, Van Bellen, Bonno, Pap, Akos F., Berkowitz, Scott D., Verhamme, Peter, Wells, Philip S., Prandoni, Paolo, Riera Mestre, Antoni, EINSTEIN CHOICE Investigators, McMaster University [Hamilton, Ontario], Klinikum Darmstadt (RMB), Klinikum Darmstadt, Carl Gustav Carus University (DRESDEN - CGCU), Technische Universität Dresden = Dresden University of Technology (TU Dresden), Service d'angiologie et d'hémostase (MR), Hôpital Universitaire de Genève, King's College Hospital (KCH), Groupe de recherche sur la thrombose (GRT (EA 3065)), Université Jean Monnet [Saint-Étienne] (UJM), University of Ottawa [Ottawa], Thromboembolism Unit (PP), Universita degli Studi di Padova, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, MUMC+: KIO Kemta (9), RS: CAPHRI - R5 - Optimising Patient Care, Epidemiologie, Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), EINSTEIN CHOICE Investigators, Bianchi, A., Brighton, T., Carroll, P., Chong, B., Chunilal, S., Coughlin, P., Curnow, J., Jackson, D., Tran, H., Ward, C., Brodmann, M., Kyrle, P., Marschang, P., Petkov, V., Hainaut, P., Jordens, P., Vandekerkhof, J., Verhamme, P., Wautrecht, J-C, Annichino-Bizzacchi, J., van Bellen, B., Correa, J., Cukier, A., Freire, A., Pereira, A., Porto, C., Sacilotto, R., Vasconcelos Costa, A., Della Siega, A., Dolan, S., Le Gal, G., Gross, P., Kahn, S., Kassis, J., Kovacs, M., Pesant, Y., Ritchie, B., Schulman, S., Shivakumar, S., Solymoss, S., Chang, S., Chen, R., Chen, Z., Chen, H., Dai, X., Fang, B., Fu, W., Gao, X., Huang, J., Lai, Y., Li, L., Li, X., Li, Y., Liu, J., Liu, S., Ma, W., Ni, S., Qin, Z., Shi, G., Tian, H., Wang, S., Wang, L., Xiao, W., Ying, K., Yu, G., Yuan, Y., Zhang, J., Zhang, X., Zhang, L., Zhu, L., Chlumský, J., Chochola, J., Dunaj, M., Kovarova, K., Lang, P., Matoška, P., Podpera, I., Spacek, R., Stehlikova, O., Brønnum-Schou, J., Egstrup, K., Gislason, G., Jeppesen, J., May, O., Nielsen, H., Wiggers, H., Achkar, A., Aquilanti, S., Benhamou, Y., Brisot, D., Bura-Riviere, A., Castella, N., Elias, A., Falvo, N., Ferrari, E., Lacroix, P., Mahe, I., Meneveau, N., Messas, E., Mismetti, P., Montaclair, K., Mottier, D., Moumneh, T., Paleiron, N., Parent, F., Pernod, G., Sanchez, O., Schmidt, J., Simoneau, G., Stephan, D., Amann, B., Bauersachs, R., Beyer-Westendorf, J., Blessing, E., Czihal, M., Espinola-Klein, C., Kahrmann, G., Licka, M., Neumeister, A., Schellong, S., Boda, Z., Farkas, K., Gurzo, M., Katona, A., Riba, M., Sipos, G., Tóth, K., Braester, A., Elias, M., Gafter-Gvili, A., Gavish, D., Hussein, O., Lishner, M., Schiff, E., Spectre, G., Tzoran-Rozenthal, I., Zimlichman, R., Ageno, W., Agnelli, G., Bova, C., Garbelotto, R., Ghirarduzzi, A., Imberti, D., Pesavento, R., Porreca, E., Visonà, A., Flota Cervera, L., Llamas Esperón, G., Rodriguez-Gonzalez, D., Solis Morales, L., Boersma, W., ten Cate, H., Erdkamp, F., Grifioen-Keijzer, A., Marwijk Kooy, M., Meijer, K., Middeldorp, S., Swart-Heikens, J., Ten Wolde, M., Westerweel, P., Braithwaite, I., Harper, P., Merriman, E., Ockelford, P., Royle, G., Smith, M., Ghanima, W., Sandset, P.M., Abola, M., Chęciński, P., Grzelakowski, P., Lewczuk, J., Sobkowicz, B., Tomkowski, W., Abramov, I., Chechulov, P., Karpenko, A., Katelnitskiy, I., Kazakov, A., Makarova, O., Panchenko, E., Sergeeva, E., Subbotin, Y., Suchkov, I., Zeltser, M., Adler, D., Breedt, J., Fourie, N., Isaacs, R., Jacobson, B., Siebert, H., van Zyl, L., Choi, J-H, Kang, S-M, Kim, K-H, Kim, H-S, Kim, D-I, Min, S-K, Park, K.H., García-Bragado Dalmau, F., Gómez Cerezo, J., Mirete, JCF, Riera, A., Del Toro, J., Eriksson, H., Torstensson, I., Banyai, M., Baumgartner, I., Mazzolai, L., Periard, D., Righini, M., Staub, D., Chiang, C-E, Chiu, K-M, Pai, P-Y, Angchaisuksiri, P., Chansung, K., Öngen, G., Tuncay, E., Alikhan, R., Chetter, I., Kesteven, P., Nokes, T., Bauer, K., Comerota, A., Elias, D., Garcia, D., Gibson, K., Ginsberg, D., Jenkins, J., Kingsley, E., Lambert, R., Lyons, R., Pullman, J., Shah, V., Smith, S.W., Stein, R., Tapson, V., Walsh, J., Wang, T-F, Do Loi, D., Do Quang, H., and Pham, N.
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Male ,[SDV]Life Sciences [q-bio] ,Phases of clinical research ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,Factor Xa Inhibitors/administration & dosage/adverse effects ,law.invention ,TOTAL KNEE ARTHROPLASTY ,0302 clinical medicine ,Randomized controlled trial ,Rivaroxaban ,ENOXAPARIN ,law ,Hemorrhage/chemically induced ,Secondary Prevention ,NONSURGICAL PATIENTS ,030212 general & internal medicine ,THROMBOPROPHYLAXIS ,ComputingMilieux_MISCELLANEOUS ,ddc:616 ,Aspirin ,Atrial fibrillation ,General Medicine ,Venous Thromboembolism ,Middle Aged ,Thrombosis ,Intention to Treat Analysis ,Anesthesia ,Adult ,Aged ,Aspirin/administration & dosage ,Aspirin/adverse effects ,Double-Blind Method ,Drug Administration Schedule ,Factor Xa Inhibitors/administration & dosage ,Factor Xa Inhibitors/adverse effects ,Female ,Humans ,Platelet Aggregation Inhibitors/administration & dosage ,Platelet Aggregation Inhibitors/adverse effects ,Rivaroxaban/administration & dosage ,Rivaroxaban/adverse effects ,Venous Thromboembolism/mortality ,Venous Thromboembolism/prevention & control ,medicine.drug ,medicine.medical_specialty ,LONG-TERM ,Platelet Aggregation Inhibitors/administration & dosage/adverse effects ,Venous Thromboembolism/mortality/prevention & control ,INTENSITY WARFARIN THERAPY ,Hemorrhage ,HIP-ARTHROPLASTY ,03 medical and health sciences ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Thromboembolism ,medicine ,Mortalitat ,Aspirina ,Mortality ,Tromboembolisme ,Intention-to-treat analysis ,business.industry ,medicine.disease ,PREVENTION ,Surgery ,Aspirin/administration & dosage/adverse effects ,Clinical trial ,THROMBOSIS ,ATRIAL-FIBRILLATION ,Rivaroxaban/administration & dosage/adverse effects ,business ,Platelet Aggregation Inhibitors ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Factor Xa Inhibitors - Abstract
Background: although many patients with venous thromboembolism require extended treatment, it is uncertain whether it is better to use full- or lower-intensity anticoagulation therapy or aspirin. Methods: in this randomized, double-blind, phase 3 study, we assigned 3396 patients with venous thromboembolism to receive either once-daily rivaroxaban (at doses of 20 mg or 10 mg) or 100 mg of aspirin. All the study patients had completed 6 to 12 months of anticoagulation therapy and were in equipoise regarding the need for continued anticoagulation. Study drugs were administered for up to 12 months. The primary efficacy outcome was symptomatic recurrent fatal or nonfatal venous thromboembolism, and the principal safety outcome was major bleeding. Results: a total of 3365 patients were included in the intention-to-treat analyses (median treatment duration, 351 days). The primary efficacy outcome occurred in 17 of 1107 patients (1.5%) receiving 20 mg of rivaroxaban and in 13 of 1127 patients (1.2%) receiving 10 mg of rivaroxaban, as compared with 50 of 1131 patients (4.4%) receiving aspirin (hazard ratio for 20 mg of rivaroxaban vs. aspirin, 0.34; 95% confidence interval [CI], 0.20 to 0.59; hazard ratio for 10 mg of rivaroxaban vs. aspirin, 0.26; 95% CI, 0.14 to 0.47; P
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- 2017
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28. Comparison of reorganized versus unaltered cardiology departments during the COVID-19 era: A subanalysis of the COV-HF-SIRIO 6 study.
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Ostrowska M, Kasprzak M, Stolarek W, Grzelakowska K, Kryś J, Kubica A, Adamski P, Podhajski P, Navarese EP, Anielska-Michalak E, Matuszewska-Brycht O, Curzytek A, Dudek A, Gromadziński L, Grzelakowski P, Kamiński L, Kleinrok A, Kostkiewicz M, Koziński M, Król P, Kulawik T, Minczew G, Mindykowski M, Pawlak A, Prokopczuk J, Skonieczny G, Sobkowicz B, Sowiński S, Stankala S, Szymański P, Wester A, Wilczewski P, Bartuś S, Budaj A, Gajda R, Gąsior M, Gruchała M, Drożdż J, Jaguszewski M, Jankowski P, Legutko J, Lesiak M, Leszek P, Mitkowski P, Nessler J, Tomaszuk-Kazberuk A, Tycińska A, Zdrojewski T, Kaźmierczak J, and Kubica J
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- Humans, Pandemics, Retrospective Studies, Hospital Mortality, COVID-19 epidemiology, Heart Failure diagnosis, Heart Failure epidemiology, Heart Failure therapy, Cardiology
- Abstract
Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, numerous cardiology departments were reorganized to provide care for COVID-19 patients. We aimed to compare the impact of the COVID-19 pandemic on hospital admissions and in-hospital mortality in reorganized vs. unaltered cardiology departments., Methods: The present research is a subanalysis of a multicenter retrospective COV-HF-SIRIO 6 study that includes all patients (n = 101,433) hospitalized in 24 cardiology departments in Poland between January 1, 2019 and December 31, 2020, with a focus on patients with acute heart failure (AHF)., Results: Reduction of all-cause hospitalizations was 50.6% vs. 21.3% for reorganized vs. unaltered cardiology departments in 2020 vs. 2019, respectively (p < 0.0001). Considering AHF alone respective reductions by 46.5% and 15.2% were registered (p < 0.0001). A higher percentage of patients was brought in by ambulance to reorganized vs. unaltered cardiology departments (51.7% vs. 34.6%; p < 0.0001) alongside with a lower rate of self-referrals (45.7% vs. 58.4%; p < 0.0001). The rate of all-cause in-hospital mortality in AHF patients was higher in reorganized than unaltered cardiology departments (10.9% vs. 6.4%; p < 0.0001). After the exclusion of patients with concomitant COVID-19, the mortality rates did not differ significantly (6.9% vs. 6.4%; p = 0.55)., Conclusions: A greater reduction in hospital admissions in 2020 vs. 2019, higher rates of patients brought by ambulance together with lower rates of self-referrals and higher all-cause in-hospital mortality for AHF due to COVID-19 related deaths were observed in cardiology departments reorganized to provide care for COVID-19 patients vs. unaltered ones.
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- 2023
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29. Longer Hospitalizations and Higher In-Hospital Mortality for Acute Heart Failure during the COVID-19 Pandemic in Larger vs. Smaller Cardiology Departments: Subanalysis of the COV-HF-SIRIO 6 Multicenter Study.
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Ostrowska M, Kasprzak M, Stolarek W, Grzelakowska K, Kryś J, Kubica A, Adamski P, Podhajski P, Navarese EP, Anielska-Michalak E, Matuszewska-Brycht O, Curzytek A, Dudek A, Gromadziński L, Grzelakowski P, Kamiński L, Kleinrok A, Kostkiewicz M, Koziński M, Król P, Kulawik T, Minczew G, Mindykowski M, Pawlak A, Prokopczuk J, Skonieczny G, Sobkowicz B, Sowiński S, Stankala S, Szymański P, Wester A, Wilczewski P, Bartuś S, Budaj A, Gajda R, Gąsior M, Gruchała M, Droźdź J, Jaguszewski M, Jankowski P, Legutko J, Lesiak M, Leszek P, Mitkowski P, Nessler J, Tomaszuk-Kazberuk A, Tycińska A, Zdrojewski T, Kaźmierczak J, and Kubica J
- Abstract
Background: The coronavirus disease-2019 (COVID-19) pandemic is surging across Poland, leading to many direct deaths and underestimated collateral damage. We aimed to compare the influence of the COVID-19 pandemic on hospital admissions and in-hospital mortality in larger vs. smaller cardiology departments (i.e., with ≥ 2000 vs. < 2000 hospitalizations per year in 2019)., Methods: We performed a subanalysis of the COV-HF-SIRIO 6 multicenter retrospective study including all patients hospitalized in 24 cardiology departments in Poland between January 1, 2019 and December 31, 2020, focusing on patients with acute heart failure (AHF) and COVID-19., Results: Total number of hospitalizations was reduced by 29.2% in larger cardiology departments and by 27.3% in smaller cardiology departments in 2020 vs. 2019. While hospitalizations for AHF were reduced by 21.8% and 25.1%, respectively. The length of hospital stay due to AHF in 2020 was 9.6 days in larger cardiology departments and 6.6 days in smaller departments ( p < 0.001). In-hospital mortality for AHF during the COVID-19 pandemic was significantly higher in larger vs. smaller cardiology departments (10.7% vs. 3.2%; p < 0.001). In-hospital mortality for concomitant AHF and COVID-19 was extremely high in larger and smaller cardiology departments accounting for 31.3% vs. 31.6%, respectively., Conclusions: During the COVID-19 pandemic longer hospitalizations and higher in-hospital mortality for AHF were observed in larger vs. smaller cardiology departments. Reduced hospital admissions and extremely high in-hospital mortality for concomitant AHF and COVID-19 were noted regardless of department size., Competing Interests: The authors declare no conflict of interest. Eliano Pio Navarese is serving as one of the Editorial Board members of this journal. We declare that Eliano Pio Navarese had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Alpo Vuorio., (Copyright: © 2022 The Author(s). Published by IMR Press.)
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- 2022
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30. Impact of COVID-19 pandemic on acute heart failure admissions and mortality: a multicentre study (COV-HF-SIRIO 6 study).
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Kubica J, Ostrowska M, Stolarek W, Kasprzak M, Grzelakowska K, Kryś J, Kubica A, Adamski P, Podhajski P, Navarese EP, Anielska-Michalak E, Brycht O, Curzytek A, Dudek A, Gromadziński L, Grzelakowski P, Kamiński L, Kleinrok A, Kostkiewicz M, Koziński M, Król P, Kulawik T, Minczew G, Mindykowski M, Pawlak A, Prokopczuk J, Skonieczny G, Sobkowicz B, Sowiński S, Stankala S, Szymański P, Wester A, Wilczewski P, Bartuś S, Budaj A, Gąsior M, Gruchała M, Drożdż J, Jaguszewski M, Jankowski P, Legutko J, Lesiak M, Leszek P, Mitkowski P, Nessler J, Tomaszuk-Kazberuk A, Tycińska A, Zdrojewski T, and Kaźmierczak J
- Subjects
- Acute Disease, Carbidopa, Drug Combinations, Humans, Levodopa analogs & derivatives, Pandemics, Retrospective Studies, SARS-CoV-2, COVID-19, Heart Failure epidemiology
- Abstract
Aims: The coronavirus disease-2019 (COVID-19) pandemic has changed the landscape of medical care delivery worldwide. We aimed to assess the influence of COVID-19 pandemic on hospital admissions and in-hospital mortality rate in patients with acute heart failure (AHF) in a retrospective, multicentre study., Methods and Results: From 1 January 2019 to 31 December 2020, a total of 101 433 patients were hospitalized in 24 Cardiology Departments in Poland. The number of patients admitted due to AHF decreased by 23.4% from 9853 in 2019 to 7546 in 2020 (P < 0.001). We noted a significant reduction of self-referrals in the times of COVID-19 pandemic accounting 27.8% (P < 0.001), with increased number of AHF patients brought by an ambulance by 15.9% (P < 0.001). The length of hospital stay was overall similar (7.7 ± 2.8 vs. 8.2 ± 3.7 days; P = not significant). The in-hospital all-cause mortality in AHF patients was 444 (5.2%) in 2019 vs. 406 (6.5%) in 2020 (P < 0.001). A total number of AHF patients with concomitant COVID-19 was 239 (3.2% of AHF patients hospitalized in 2020). The rate of in-hospital deaths in AHF patients with COVID-19 was extremely high accounting 31.4%, reaching up to 44.1% in the peak of the pandemic in November 2020., Conclusions: Our study indicates that the COVID-19 pandemic led to (i) reduced hospital admissions for AHF; (ii) decreased number of self-referred AHF patients and increased number of AHF patients brought by an ambulance; and (iii) increased in-hospital mortality for AHF with very high mortality rate for concomitant AHF and COVID-19., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)
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- 2022
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31. A new approach to ticagrelor-based de-escalation of antiplatelet therapy after acute coronary syndrome. A rationale for a randomized, double-blind, placebo-controlled, investigator-initiated, multicenter clinical study.
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Kubica J, Adamski P, Niezgoda P, Kubica A, Podhajski P, Barańska M, Umińska JM, Pietrzykowski Ł, Ostrowska M, Siller-Matula JM, Badarienė J, Bartuś S, Budaj A, Dobrzycki S, Fidor Ł, Gąsior M, Gessek J, Gierlotka M, Gil R, Gorący J, Grzelakowski P, Hajdukiewicz T, Jaguszewski M, Janion M, Kasprzak J, Kern A, Klecha A, Kleinrok A, Kochman W, Krakowiak B, Legutko J, Lesiak M, Nosal M, Piotrowski G, Przybylski A, Roleder T, Skonieczny G, Sobieszek G, Tycińska A, Wojciechowski D, Wojakowski W, Wójcik J, Zielińska M, Żurakowski A, Specchia G, Gorog DA, and Navarese EP
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- Aspirin, Humans, Platelet Aggregation Inhibitors, Ticagrelor, Acute Coronary Syndrome diagnosis, Acute Coronary Syndrome drug therapy, Percutaneous Coronary Intervention
- Abstract
The risk of ischemic events gradually decreases after acute coronary syndrome (ACS), reaching a stable level after 1 month, while the risk of bleeding remains steady during the whole period of dual antiplatelet treatment (DAPT). Several de-escalation strategies of antiplatelet treatment aiming to enhance safety of DAPT without depriving it of its efficacy have been evaluated so far. We hypothesized that reduction of the ticagrelor maintenance dose 1 month after ACS and its continuation until 12 months after ACS may improve adherence to antiplatelet treatment due to better tolerability compared with the standard dose of ticagrelor. Moreover, improved safety of treatment and preserved anti-ischemic benefit may also be expected with additional acetylsalicylic acid (ASA) withdrawal. To evaluate these hypotheses, we designed the Evaluating Safety and Efficacy of Two Ticagrelor-based De-escalation Antiplatelet Strategies in Acute Coronary Syndrome - a randomized clinical trial (ELECTRA-SIRIO 2), to assess the influence of ticagrelor dose reduction with or without continuation of ASA versus DAPT with standard dose ticagrelor in reducing clinically relevant bleeding and maintaining anti-ischemic efficacy in ACS patients. The study was designed as a phase III, randomized, multicenter, double-blind, investigator-initiated clinical study with a 12-month follow-up (ClinicalTrials.gov Identifier: NCT04718025; EudraCT number: 2020-005130-15).
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- 2021
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32. The effects of percutaneous transluminal coronary intervention on biomarkers of oxidative stress in the erythrocytes of elderly male patients.
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Szewczyk-Golec K, Grzelakowski P, Ługowski T, and Kędziora J
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- Aged, Angina Pectoris blood, Angina Pectoris therapy, Antioxidants metabolism, Catalase blood, Coronary Angiography, Glutathione blood, Glutathione Peroxidase blood, Humans, Lipid Peroxidation, Male, Malondialdehyde blood, Middle Aged, Oxidative Stress, Superoxide Dismutase blood, Angioplasty, Balloon, Coronary, Myocardial Ischemia blood, Myocardial Ischemia therapy
- Abstract
Objectives: Oxidative stress plays a key role in the pathogenesis of coronary artery disease. The aim of this study was to compare the effects of percutaneous transluminal coronary angioplasty (PTCA) and elective coronary angiography (EC) on erythrocytic antioxidant defense in elderly male patients., Methods: Twenty-three stable angina pectoris (SAP) patients undergoing PTCA and 18 patients with ischemic symptoms scheduled to undergo diagnostic EC were included in the study. The concentrations of malondialdehyde (MDA) and reduced glutathione (GSH) and the activities of Zn,Cu-superoxide dismutase (SOD-1), catalase (CAT), and cytosolic glutathione peroxidase (GSH-Px) were examined in the erythrocytes before, immediately after and 2 weeks following PTCA or EC., Results: The MDA concentrations were significantly higher and SOD-1, CAT, and GSH-Px activities were significantly lower in the PTCA group than in the EC group at baseline. Two weeks after treatment, the activities of the enzymes significantly increased in both groups, whereas the MDA concentrations decreased only in the PTCA patients., Conclusions: The results confirm that an advanced state of atherosclerosis is related to greater levels of oxidative stress. The study indicates that both procedures may induce antioxidant defenses; however, PTCA exclusively induces a long-term reduction in lipid peroxidation.
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- 2017
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33. [Acute intermediate-risk pulmonary embolism with right-sided free-floating intracardiac thrombus, systemic inflammatory reaction syndrome, multiple organ dysfunction syndrome, disseminated intravascular coagulation and acute ischaemia of a limb].
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Grzelakowski P, Lugowski T, Kurzyna M, Missima M, Maciejewski M, Balcerzak M, Romanek R, Stelak M, Lugowski A, and Goch A
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- Coronary Thrombosis complications, Coronary Thrombosis therapy, Disseminated Intravascular Coagulation complications, Disseminated Intravascular Coagulation therapy, Edema complications, Edema, Cardiac etiology, Edema, Cardiac therapy, Female, Humans, Ischemia complications, Ischemia diagnosis, Leg blood supply, Microvessels physiopathology, Middle Aged, Multiple Organ Failure etiology, Multiple Organ Failure therapy, Pulmonary Embolism etiology, Pulmonary Embolism therapy, Systemic Inflammatory Response Syndrome complications, Systemic Inflammatory Response Syndrome therapy, Coronary Thrombosis diagnosis, Disseminated Intravascular Coagulation diagnosis, Edema, Cardiac diagnosis, Multiple Organ Failure diagnosis, Pulmonary Embolism diagnosis, Systemic Inflammatory Response Syndrome diagnosis
- Abstract
A case of a 64 year-old woman admitted to ICCU because of severe dyspnoea and oedema of left lower limb is presented. We diagnosed coincidence of acute pulmonary embolism with right-sided free-floating heart thrombi, systemic inflammatory reaction syndrome, multiple organ dysfunction syndrome, disseminated intravascular coagulation and acute ischaemia of the right lower limb. Due to atypical clinical presentation therapeutic strategies were discussed with ZATPOL registry coordinator. The patient was treated pharmacologically, underwent cardiosurgical evacuation of right-sided intracardiac thrombus and lower limb amputation. At follow up visit 6 months after discharge from hospital she was in good general condition with no complaints.
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- 2010
34. ['Protective' stent implantation in a patient with acute coronary syndrome without ST segment elevation complicated by in stent thrombosis].
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Romanek R, Grzelakowski P, Formuszewicz R, Ługowski T, Wnuk T, Olechnicki M, Rusicka-Piekarz T, and Goch A
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- Coronary Angiography, Coronary Thrombosis diagnostic imaging, Female, Humans, Middle Aged, Acute Coronary Syndrome therapy, Coronary Thrombosis etiology, Stents adverse effects
- Published
- 2010
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