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Comparison of fatal or irreversible events with extended-duration betrixaban versus standard dose enoxaparin in acutely Ill medical patients: An APEX trial substudy

  • C. Michael Gibson
  • , Serge Korjian
  • , Gerald Chi
  • , Yazan Daaboul
  • , Purva Jain
  • , Douglas Arbetter
  • , Samuel Z. Goldhaber
  • , Russel Hull
  • , Adrian F. Hernandez
  • , Renato D. Lopes
  • , Alex Gold
  • , Alexander T. Cohen
  • , Robert A. Harrington
  • , F. Bello
  • , A. E. Ferrari
  • , H. Jure
  • , S. Macin
  • , M. Oliva
  • , M. Parody
  • , C. Poy
  • R. Baker, D. Colquhoun, P. Coughlin, S. Finfer, G. Hammerschlag, A. Rubinfeld, K. Huber, J. König, R. Mathies, E. Pilger, H. Schoenerr, I. Adzerikho, V. Koryk, E. Mikhailova, N. Mitkovskaya, S. Pimanov, L. Polonetsy, N. Soroka, D. Blockmans, M. Delforge, A. Dive, F. Lienart, S. Motte, J. Annichino Bizzacchi, E. Fiss, A. Freire, E. Manenti, E. Ramacciotti, S. Raymuno, A. Rocha, J. F. Saraiva, B. Dimov, M. Grigorov, R. Kalpachki, Z. Kamenova, M. Kostadinova, M. Milanova, V. Mincheva, G. Pencheva, D. Raev, N. Runev, N. Stoeva, M. Stoyanov, S. Syulemzova, G. Todorov, M. Tokmakova, A. Dhar, J. Douketis, S. Kahn, G. Le Gal, M. Pearce, S. Provencher, S. Verreault, M. Arias Alarcon, C. Olivares Cañon, M. Opazo Lazcano, S. Potthoff Cardenas, S. Butkovic-Soldo, S. Car, N. Ciglenecki, I. Francetic, M. Jakopovic, H. Kalinic-Grgorinic, A. Knezevic, B. Malojcic, S. Marusic, J. Sikic Vagic, V. Skerk, O. Cermak, P. Cervinka, J. Chlumsky, J. Chochola, V. Cizek, M. Dunaj, J. Dusek, L. Francek, J. Havelka, M. Herold, R. Holaj, I. Horny, J. Hubac, P. Jajtner, P. Kolman, P. Lang, O. Mayer, J. Mikulova, I. Podpera, P. Reiterer, R. Spacek, J. Vejvoda, M. Vyhnanek, H. Christensen, M. Lassen, M. Storgaard, C. Tuxen, S. Urhammer, M. Lember, T. Marandi, T. Uuetoa, J. Airaksinen, J. Honkaniemi, R. Kaaja, R. Lassila, J. Saarinen, T. Tatlisumak, S. Vikman, B. Agraou, S. Aquilanti, A. Belhassane, D. Brisot, G. De Geeter, P. Debourdeau, E. Decoulx, D. El Kouri, N. Falvo, C. Grange, P. Lacroix, E. Messas, P. Mismetti, K. Montaclair, D. Mottier, N. Paleiron, L. Payot, G. Pernod, P. Pottier, A. Proust, I. Quere, P. M. Roy, J. Schmidt, G. Simoneau, I. Datikashvili-David, G. Khabeishvili, I. Khintibidze, B. Kobulia, I. Megreladze, Z. Pagava, K. Paposhvili, T. Shaburishvili, B. Amann, J. Berrouschot, J. Beyer-Westendorf, E. Blessing, M. Bott, T. Dengler, C. Diehm, R. Dziewas, S. Genth-Zotz, F. Hamann, T. Horacek, S. Klimpe, R. Kröning, H. Lapp, H. Lawall, M. Licka, T. Rizos, S. Schellong, J. Schmidt-Lucke, C. Singer, C. Tiefenbacher, R. Veltkamp, C. Weimar, U. Zeymer, B. Alkonyi, J. Faluközy, L. Futo, A. Katona, R. Kirschner, P. Kristóf, F. Lakatos, Z. Laszlo, G. Lupkovics, B. Merkely, C. Nagy András, L. Németh, A. Papp, P. Soltesz, Z. Sudár, G. Szabo, N. Szegedi, G. Tímár, J. Valcó, A. Vertes, S. Efrati, M. Elias, A. Gafter, T. Hayek, O. Hussein, M. Lishner, G. Lugassy, D. Zeltser, W. Ageno, I. Cerveri, A. D'Angelo, A. De Pellegrin, D. Imberti, Raffaele Landolfi, G. Lembo, C. Lodigiani, M. Luisetti, M. Moia, M. Molteni, N. Mumoli, S. Novo, F. Orlandini, R. Parisi, A. Pizzini, F. Pomero, A. Salvi, A. Schenone, A. Visonà, D. Krievins, V. Martinova, N. Pontaga, V. Rozitis, I. Stukena, B. Alekniene, A. Bagdonas, V. Basijokiene, Z. Butkiene, V. Griskeviciene, A. Naudziunas, R. Norvaisiene, R. Norviliene, R. Petrauskiene, R. Poskiene, D. Susinskiene, A. Valavicius, R. Castillo Leon, R. Cotrina Pereyra, L. Farjardo Karlo, M. Horna, J. Lema Osores, M. Salas, L. Toche Yañez, W. Fryze, Z. Gaciong, J. Gniot, D. Gorecka, P. Gruenpeter, P. Grzelakowski, D. Jastrzebski, L. Kucharski, E. Mirek-Bryniarska, G. Pulkowski, B. Sobkowicz, P. Sulik, W. Tomkowski, L. Walasek, K. Waldemar, K. Wrzesinski, Z. E. Balogh, M. Bojinca, I. Marin, S. Mot, R. Musetescu, C. Podoleanu, M. Popescu, S. Stamate, G. Stanciulescu, L. Vida-Simiti, A. Abashev, D. Andreev, K. Apartsin, M. Arkhipov, O. Averkov, O. Barbarash, G. Belskaya, E. Bogdanov, S. Boldueva, Z. Chefranova, Y. Dovgalevskiy, O. Ershova, B. Goloshchekin, N. Khachatryan, E. Khurs, G. Klein, Z. Kobalava, E. Kosmacheva, V. Kostenko, A. Malygin, T. Martynenko, V. Martynenko, N. Maslova, V. Mordovin, K. Nikolaev, R. Nilk, E. Panchenko, D. Popov, E. Privalova, O. Reshetko, E. Sergeeva, Y. Shapovalova, L. Shpagina, Y. Shvarts, V. Simanenkov, O. Solovyov, E. Vishneva, A. Vishnevskiy, S. Apostolovic, V. Celic, S. Ilic, A. Kovacevic-Kuzmanovic, V. Miloradovic, R. S. Tan, S. Bodikova, A. Cervenakova, M. Dvorak, L. Gaspar, O. Herman, A. Hrubon, M. Kokles, G. Krastev, J. Payer, D. Prokop, M. Spisakova, D. Adler, M. Basson, J. Breedt, J. Engelbrecht, B. Jacobson, I. Mitha, C. Van Dyk, L. A. Alvarez Sala, C. Barbagelata López, J. Bisbe, A. Castro Guardiola, J. M. Cepeda, F. Cereto, E. Diaz Santos, R. Ferrer, J. Gomez Cerezo, J. R. Gonzales-Porras, J. Grandes, D. Jiménez, I. Martín Loeches, L. Mellibovsky, C. Richart, A. Riera, J. Trujillo, J. A. Vargas Nunez, J. Villalta, O. Akgul, S. Guneri, K. Kilichesmez, C. Kirma, H. Kutluk, B. Nazliel, G. Okumus, G. Ongen, K. Tigen, M. Topcuoglu, E. Tuncay, O. Abrahamovych, V. Batushkin, J. Brozhyk, I. Burmak, O. Godlevska, A. Goloborodko, B. Goloborodko, Y. Goncharova, V. Gryb, O. Karpenko, M. Kopytsya, V. Koshlia, O. Krakhmalova, I. Kyrychenko, O. Legkonogov, Y. Malynovsky, V. Maslovaskyi, V. Nikonov, O. Parkhomenko, M. Perepeliuk, D. Reshotko, L. Rudenko, T. Ryabichenko, I. Svyridova, Y. Svyshchenko, V. Tseluyko, G. Ursol, I. Vakaliuk, I. Vishnivestsky, L. Voronkov, A. Yagensky, R. Body, D. Chandra, M. Davis, P. Kesteven, P. Maccallum, C. Mccollum, I. Natarajan, E. Almasri, M. Amin, C. Anderson, S. Baker, J. Barney, B. Barth A. Bastani, P. Bercz, M. Bidair, T. Carman, H. Chang, C. Clark, M. Concha, J. Cornell, R. Dhingra, A. Doshi, R. Ebrahimi, B. Farley, G. Fermann, G. Foster, J. Fraiz, J. Fulmer, H. Gaggin, D. Goytia-Leos, B. Hahn, A. Haidar, A. Hamad, M. Hazelrigg, O. Ioachimescu, B. Johnson, H. Kabler, C. K. Kao, M. Kazimir, F. Kouras, M. Kung, R. Lerner, J. Lopez, A. Macchiavelli, S. Mahal, B. Margolis, G. Mclaren, T. Milling, M. Mittal, V. Nadar, V. Ohaju, T. Ortel, J. Overcash, K. Parthiban, R. Pearl, L. Pineda, R. Pratt, J. Pullman, O. Quintana, R. Rajan, P. Rastogi, C. Rees, W. Rodriguez, F. Saba, N. Shammas, S. Sharma, S. Sokol, S. Stoltz, D. Subich, M. Tuck, J. Updegrove, A. Warner, M. Welch, J. Welker, B. Whitman, T. Wichman, K. Yousef, R. Yusen, N. Zakai
  • Harvard University
  • University of Calgary
  • Duke University
  • Portola Pharmaceuticals Inc.
  • Guy’s & St Thomas’ NHS FT
  • Stanford University

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)N/A-N/A
JournalJOURNAL OF THE AMERICAN HEART ASSOCIATION. CARDIOVASCULAR AND CEREBROVASCULAR DISEASE
Volume6
DOIs
Publication statusPublished - 2017

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Keywords

  • Acute Disease
  • Adult
  • Aged
  • Anticoagulants
  • Benzamides
  • Cardiovascular Diseases
  • Death
  • Double-Blind Method
  • Enoxaparin
  • Factor Xa Inhibitors
  • Female
  • Hemorrhage
  • Humans
  • Inpatients
  • Intracranial Hemorrhages
  • Intracranial hemorrhage
  • Ischemic stroke
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Myocardial infarction
  • Proportional Hazards Models
  • Pulmonary embolism
  • Pyridines
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Venous Thromboembolism
  • Venous thromboembolism

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