Enoxaparin followed by once-weekly idrabiotaparinux versus enoxaparin plus warfarin for patients with acute symptomatic pulmonary embolism: a randomised, double-blind, double-dummy, non-inferiority trial
| Autor: | Büller, Hr, Gallus, As, Prins, Mh, Raskob, G, Decousus, H, Charbonnier, B, Leizorovicz, A, Laporte, S, Quenet, S, Brandjes, Dp, Middeldorp, S, Blüguermann, J, Amuchastegui, L, Ahuad Guerrero, R, Oberti, P, Alvarez, C, Cassettari, A, Santos, D, Macin, S, Santini, F, Ward, C, Coughlin, P, Salem, H, Gan, E, Leyden, M, Prosser, I, Crispin, P, Carroll, P, Gallus, A, Mcrae, S, Waites, J, Pilger, E, Koppensteiner, R, Kyrle, P, Schinko, H, Mrochek, A, Mitkovskaya, N, Prystrom, A, Motte, S, Ninane, V, Delcroix, M, Hainaut, P, Schneider, E, Saraiva, J, Maia, L, Barreto, S, Fernandes Manenti, E, Araujo, G, Dutra, O, Fiss, E, Moreira, R, Yankov, K, Nenkova, S, Ivanov, Y, Kostov, V, Bhargava, R, Chan, Y, Miron, Mj, Cusson, J, Ugarte, S, Morales, A, Andresen, M, Lanas, F, Arriagada, G, Mendoza, Jj, Zuñiga, C, Sepulveda, P, Wang, C, Liu, Z, Yuan, Y, Ma, Z, Fang, B, Liu, J, Bai, C, Wu, H, Yang, L, Ying, K, Kang, J, Li, Q, Cheng, Z, Zhang, J, Wang, H, Xie, C, Xia, G, Du, Y, Wu, Q, Zhou, X, Chen, L, Yi, Q, Wu, C, Hao, Q, Liu, S, Xiong, S, Jiang, S, Zhao, L, Xiao, Q, Qin, Z, Zhou, J, Dennis, R, Miserque, N, Igueredo, M, Londoño, D, Hildebrando, J, Granados, M, Buitrago, R, Solano, Mh, Pacheco Alvis PM, Botero, R, Saenz, O, Bergovec, M, Padovan, M, Vucic, N, Samarzija, M, Chlumsky, J, Spacek, R, Klimsa, Z, Gregor, P, Povolny, J, Podpera, I, Holm, F, Lang, P, Matoska, P, Sabl, P, Spinar, J, Spac, J, Husted, S, Avnstrom, S, Rasmussen, S, Christensen, A, Guindy, R, Hassanein, M, Paumets, M, Meriste, S, Ferrari, E, Achkar, A, Azarian, R, Meneveau, N, Lorut, C, Mouallem, J, Crestani, B, Proton, A, Salmeron, S, Lerousseau, L, Mottier, D, Wahl, D, Siafakas, N, Papadimitriou, D, Katis, K, Katsaris, G, Gaga, A, Damianos, A, Tipparaju, S, Kalkunte, S, Vidhut, J, Kalashetti, S, Mehta, P, Talwar, D, Ramanathan, R, Mishra, R, Zeltzer, D, Lahav, M, Brenner, B, Caraco, Y, Elias, M, Piovella, F, Barone, M, Poggio, R, Palla, A, Ghirarduzzi, A, Pini, M, Lodigiani, C, Prandoni, Paolo, Agnelli, G, Imberti, D, Scannapieco, G, Salvi, A, Bautista, E, Diaz, J, Mercado, R, Ranero, A, Rodriguez, D, Jerjes, C, Villeda Espinoza, E, Van Der Meer, J, Ijfering, W, Van Marwijk Kooy, M, Boersma, W, Van Leendert, R, Kroon, C, Dullemond Westland, A, Viergever, P, Kuipers, A, Grootenboers, M, Creemers, J, Pieters, W, De Munck, D, Timmer, H, Jackson, S, Sandset, P, Meyer, P, Kristiansen, T, Portugal, J, Paz, E, Salazar, D, Chavez, W, Castillo, L, De Guia, T, Lenora, F, Tomkowski, W, Kloczko, J, Rybak, Z, Gaciong, Z, Sobkowicz, B, Pruszczyk, P, Nizankowski, R, Mirek Bryniarska, E, Kukla, P, Reis, A, França, A, Cortez, M, Sa, J, Santos, F, Marques, Ma, Gordeev, I, Gendlin, G, Yablonsky, P, Sokurenko, G, Soroka, V, Lusov, V, Markov, V, Shvats, Y, Katerlnitskiy, I, Lapin, O, Lyamina, N, Subbotin, Y, Kim, I, Zilber, E, Kchaisheva, L, Poliacik, P, Macek, V, Pretorius, Jp, Abdullah, I, Basson, M, Bollinger, C, Breedt, J, Gani, M, Jansen, J, Le Roux, G, Nortje, H, Van Der Linder, M, Van Zyl, L, Viljoen, J, Bruning, A, Pujol Farriols, R, Raguer, E, Nuffal, D, Sanchez Rodriguez, A, Eriksson, H, Almgren, T, Carlsson, A, Elf, J, Olsson, Cg, Aagesen, J, Savas, I, Sahin, A, Erdogan, Y, Ozhan, M, Ongen, G, Celikel, T, Turker, H, Arseven, O, Tuncay, E, Ozacar, R, Gudz, I, Nykonenko, O, Skupyy, O, Kovalskyy, I, Prasol, V, Cohen, A, Rodriguez Cintron, W, Gurka, D, Bradley, J, Oliver, G, Spyropoulos, A, Lerner, R, Fulmer, J, Lu, Np, Wright, P, Han, D, Servi, R, Nadar, V, Quaranta, A, Gehring, J, Ginsberg, R, Jacobson, A, Colan, D, Vanway, C, Gurza, E, Braslow, B, Shorr, A, Rehm, J, Martin, J, Sellers, M, Concha, M, Gordon, I, Pullman, J, Moran, J, Welker, J, Panzarella, P, Mullins, M, Willms, D, Mcgrew, F, Turki, M, Menajovsky, L. |
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| Přispěvatelé: | Epidemiologie, MUMC+: KIO Kemta (9), RS: CAPHRI School for Public Health and Primary Care, Amsterdam Cardiovascular Sciences, Vascular Medicine, Department of Vascular Medicine (DVM - AMC), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), SA Pathology at Flinders Medical Center (ASG), Flinders University, Department of Epidemiology (MHP), Maastricht University [Maastricht], College of Public Health (CPH), University of Oklahoma (OU), 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) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
MESH: Pulmonary Embolism Oligosaccharides MESH: Factor X 030204 cardiovascular system & hematology MESH: Intention to Treat Analysis MESH: Aged 80 and over 0302 clinical medicine MESH: Double-Blind Method 030212 general & internal medicine MESH: Warfarin Aged 80 and over MESH: Aged education.field_of_study Idrabiotaparinux MESH: Middle Aged General Medicine Heparin Middle Aged Intention to Treat Analysis 3. Good health Pulmonary embolism Acute Disease MESH: Acute Disease Drug Therapy Combination Female medicine.drug Adult medicine.medical_specialty MESH: Enoxaparin Adolescent Population Biotin MESH: Anticoagulants Double blind 03 medical and health sciences Double-Blind Method Internal medicine MESH: Biotin medicine Humans Enoxaparin education Aged MESH: Adolescent MESH: Humans Intention-to-treat analysis business.industry Warfarin Anticoagulants MESH: Adult Odds ratio medicine.disease MESH: Male Surgery MESH: Drug Therapy Combination Factor X Pulmonary Embolism business MESH: Female MESH: Oligosaccharides [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | Lancet, 379(9811), 123-129. Elsevier Science Lancet, 379(9811), 123-129. Elsevier Limited Lancet Lancet, Elsevier, 2012, 379 (9811), pp.123-9. ⟨10.1016/S0140-6736(11)61505-5⟩ |
| ISSN: | 0140-6736 1474-547X |
| DOI: | 10.1016/S0140-6736(11)61505-5⟩ |
| Popis: | International audience; BACKGROUND: Treatment of pulmonary embolism with low-molecular-weight heparin and vitamin K antagonists, such as warfarin, is not ideal. We aimed to assess non-inferiority of idrabiotaparinux, a reversible longlasting indirect inhibitor of activated factor X, to warfarin in patients with acute symptomatic pulmonary embolism. METHODS: In our randomised, double-blind, double-dummy, non-inferiority trial, we enrolled adults with objectively documented acute symptomatic pulmonary embolism attending 291 centres in 37 countries. We excluded patients who were pregnant, had active bleeding, kidney failure, or malignant hypertension, or were at high risk of death, bleeding, or adverse reactions to study drugs. We randomly allocated patients to receive 5-10 days' enoxaparin 1*0 mg/kg twice daily followed by subcutaneous idrabiotaparinux (starting dose 3*0 mg) or adjusted-dose warfarin (target international normalised ratio 2*0-3*0); regimens lasted 3 months or 6 months dependent on clinical presentation. Block randomisation was done with a central interactive computerised system, stratified by study centre and intended treatment duration. The primary efficacy outcome was recurrent venous thromboembolism at 99 days after randomisation. We estimated the odds ratio and 95% CI with a Mantel-Haenzsel χ(2) analysis (non-inferiority margin 2*0) in the intention-to-treat population. The main safety outcome was clinically relevant bleeding (major or non-major) in all patients at day 99. This study is registered with ClinicalTrials.gov, number NCT00345618. FINDINGS: Between Aug 1, 2006, and Jan 31, 2010, we enrolled 3202 patients aged 18-96 years. 34 (2%) of 1599 patients randomly allocated to receive enoxaparin-idrabiotaparinux and 43 (3%) of 1603 patients randomly allocated to receive enoxaparin-warfarin had recurrent venous thromboembolism (odds ratio 0*79, 95% CI 0*50-1*25; p(non-inferiority)=0*0001). 72 (5%) of 1599 patients in the enoxaparin-idrabiotaparinux group and 106 (7%) of 1603 patients in the enoxaparin-warfarin group had clinically relevant bleeding (0*67, 0*49-0*91; p(superiority)=0*0098). We noted similar differences in outcomes in those patients treated to 6 months. INTERPRETATION: Idrabiotaparinux could provide an attractive alternative to warfarin for the long-term treatment of pulmonary embolism, and seems to be associated with reduced bleeding. FUNDING: Sanofi-Aventis (Paris, France). |
| Databáze: | OpenAIRE |
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