1. Comparison of Fatal or Irreversible Events With Extended-Duration Betrixaban Versus Standard Dose Enoxaparin in Acutely III Medical Patients: An APEX Trial Substudy
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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.
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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