Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis
Sam Schulman, Ajay K Kakkar, Samuel Z Goldhaber, Sebastian Schellong, Henry Eriksson, Patrick Mismetti, Anita Vedel Christiansen, Jeffrey Friedman, Florence Le Maulf, Nuala Peter, Clive Kearon, RE-COVER II Trial Investigators, S Schulman, H Eriksson, S Goldhaber, A Kakkar, C Kearon, P Mismetti, S Schellong, D Bergqvist, J Tijssen, M Prins, S Robben, H Büller, H M Otten, D Brandjes, M Prins, H Büller, H M Otten, D Brandjes, M Prins, R Peters, M R Mac Gillavry, E Gan, H Salem, R Baker, P Blomberry, J Curnow, J M Annichino-Bizzacch, M D Brandao Panico, J R Timi Ribas, E R Fernandes Manenti, F Miranda Jr, J Moraes Jr, D Raev, M Mollov, M Peneva, S Milanov, D Anderson, M Crowther, S Dolan, J Eikelboom, M Game, S Kahn, J Kassis, C Kearon, B Ritchie, S Solymoss, M Rodger, E Yeo, A Milot, P Klinke, W Chen, L Zhihong, B Chunxue, L Jinming, Z Jiwei, C Jie, K Jina, W Yuqi, Y Zhongqi, W Hua, Y Kejing, L Bonan, Y Yadong, L Changwei, Z Jin, D Yongcheng, J Spinar, R Maly, V Cizek, J Bercikova, P Cervinka, P Lang, V Jirka, I Oral, P Reichert, L Kotik, S Pojsl, T Klimovic, S Husted, H Nielsen, E Friis, K Skødebjerg Kristensen, D Mottier, P Mismetti, D El Kouri, Y Bleher, L Leroux, Z Boda, M Sereg, M Riba, J S Hiremath, S Kareem, D N Banker, M Gadkari, R Parakh, K R Suresh, S Natarajan, A Jain, P K Aggarwal, C B Patil, N Durairaj, R Seshadri, V M Thakore, K M Rai, S Efrati, M Elias, D Gavish, M Grossman, M Lishner, M Lahavr, G Lugassy, W Nseir, D Zeltser, B Brenner, S Yeganeh, N Zanatta, A M Pizzini, M Di Salvo, S Novo, E Arosio, M Campanini, S Castellani, D Y Oh, D K Cho, D I Kim, T W Kwon, S S Yoon, M H Kim, S Y Kwon, J W Cheong, T S Lee, A A Shokri, T S Looi, Y Chon, K Y Chunn, R Salleh, R Fijnheer, G Veth, A Dees, H Pruijt, A G Lieverse, G K S Jie, M van Marwijk-Kooij, S Simsek, M Hanna, S Jackson, P Ockelford, M Smith, P M Sandset, A Waage, L Fernandez, A Ma, T De Guia, H Ong-Garcia, L Lach, K Zawilska, S Gluszek, K Czarnobilski, Z Gaciong, M Chernyatina, A Tchumakov, I Staroverov, S Belentsov, I Katelnitsky, A Khamitov, A Zaporozhsky, M Degterev, A Khitaryan, L L Heng, P A Robless, S Y K Kenny, P Poliacik, T Duris, M Szentivanyi, V Zubek, D Adler, C Smith, D Le Roux, J Van Rensburg, D Miller, S Ismail, A Roodt, I H Vermooten, J Villalta, J A Nieto, J Trujillo, J del Toro, M J García Fuster, A Giménez, P Lozano, M Holmström, H Eriksson, M Edmark, A Carlsson, I Torstensson, C H Huang, K G Shyu, C E Chiang, M C Shen, C S Tsai, S S Wang, C Sirijerachai, S Saetang, N Kanitsap, C Polprasert, P Mutirangura, S Boonbaichaiyapruck, A Leelasiri, M Kurtoglu, E Eren, U Bengisun, U Sakinci, S Karahan, F Islamoglu, N Kurt, E Aygun, O Skupyy, D Keeling, P Kesteven, A Cohen, R Maclean, W Thomas, J A Masson, E Bolster, T Beard, A Gasparis, L M LaPerna, K Gibson, B Curtis, C O Chu, P Bass 3rd, R Lavende, Sam Schulman, Ajay K Kakkar, Samuel Z Goldhaber, Sebastian Schellong, Henry Eriksson, Patrick Mismetti, Anita Vedel Christiansen, Jeffrey Friedman, Florence Le Maulf, Nuala Peter, Clive Kearon, RE-COVER II Trial Investigators, S Schulman, H Eriksson, S Goldhaber, A Kakkar, C Kearon, P Mismetti, S Schellong, D Bergqvist, J Tijssen, M Prins, S Robben, H Büller, H M Otten, D Brandjes, M Prins, H Büller, H M Otten, D Brandjes, M Prins, R Peters, M R Mac Gillavry, E Gan, H Salem, R Baker, P Blomberry, J Curnow, J M Annichino-Bizzacch, M D Brandao Panico, J R Timi Ribas, E R Fernandes Manenti, F Miranda Jr, J Moraes Jr, D Raev, M Mollov, M Peneva, S Milanov, D Anderson, M Crowther, S Dolan, J Eikelboom, M Game, S Kahn, J Kassis, C Kearon, B Ritchie, S Solymoss, M Rodger, E Yeo, A Milot, P Klinke, W Chen, L Zhihong, B Chunxue, L Jinming, Z Jiwei, C Jie, K Jina, W Yuqi, Y Zhongqi, W Hua, Y Kejing, L Bonan, Y Yadong, L Changwei, Z Jin, D Yongcheng, J Spinar, R Maly, V Cizek, J Bercikova, P Cervinka, P Lang, V Jirka, I Oral, P Reichert, L Kotik, S Pojsl, T Klimovic, S Husted, H Nielsen, E Friis, K Skødebjerg Kristensen, D Mottier, P Mismetti, D El Kouri, Y Bleher, L Leroux, Z Boda, M Sereg, M Riba, J S Hiremath, S Kareem, D N Banker, M Gadkari, R Parakh, K R Suresh, S Natarajan, A Jain, P K Aggarwal, C B Patil, N Durairaj, R Seshadri, V M Thakore, K M Rai, S Efrati, M Elias, D Gavish, M Grossman, M Lishner, M Lahavr, G Lugassy, W Nseir, D Zeltser, B Brenner, S Yeganeh, N Zanatta, A M Pizzini, M Di Salvo, S Novo, E Arosio, M Campanini, S Castellani, D Y Oh, D K Cho, D I Kim, T W Kwon, S S Yoon, M H Kim, S Y Kwon, J W Cheong, T S Lee, A A Shokri, T S Looi, Y Chon, K Y Chunn, R Salleh, R Fijnheer, G Veth, A Dees, H Pruijt, A G Lieverse, G K S Jie, M van Marwijk-Kooij, S Simsek, M Hanna, S Jackson, P Ockelford, M Smith, P M Sandset, A Waage, L Fernandez, A Ma, T De Guia, H Ong-Garcia, L Lach, K Zawilska, S Gluszek, K Czarnobilski, Z Gaciong, M Chernyatina, A Tchumakov, I Staroverov, S Belentsov, I Katelnitsky, A Khamitov, A Zaporozhsky, M Degterev, A Khitaryan, L L Heng, P A Robless, S Y K Kenny, P Poliacik, T Duris, M Szentivanyi, V Zubek, D Adler, C Smith, D Le Roux, J Van Rensburg, D Miller, S Ismail, A Roodt, I H Vermooten, J Villalta, J A Nieto, J Trujillo, J del Toro, M J García Fuster, A Giménez, P Lozano, M Holmström, H Eriksson, M Edmark, A Carlsson, I Torstensson, C H Huang, K G Shyu, C E Chiang, M C Shen, C S Tsai, S S Wang, C Sirijerachai, S Saetang, N Kanitsap, C Polprasert, P Mutirangura, S Boonbaichaiyapruck, A Leelasiri, M Kurtoglu, E Eren, U Bengisun, U Sakinci, S Karahan, F Islamoglu, N Kurt, E Aygun, O Skupyy, D Keeling, P Kesteven, A Cohen, R Maclean, W Thomas, J A Masson, E Bolster, T Beard, A Gasparis, L M LaPerna, K Gibson, B Curtis, C O Chu, P Bass 3rd, R Lavende
Abstract
Background: Dabigatran and warfarin have been compared for the treatment of acute venous thromboembolism (VTE) in a previous trial. We undertook this study to extend those findings.
Methods and results: In a randomized, double-blind, double-dummy trial of 2589 patients with acute VTE treated with low-molecular-weight or unfractionated heparin for 5 to 11 days, we compared dabigatran 150 mg twice daily with warfarin. The primary outcome, recurrent symptomatic, objectively confirmed VTE and related deaths during 6 months of treatment occurred in 30 of the 1279 dabigatran patients (2.3%) compared with 28 of the 1289 warfarin patients (2.2%; hazard ratio, 1.08; 95% confidence interval [CI], 0.64-1.80; absolute risk difference, 0.2%; 95% CI, -1.0 to 1.3; P<0.001 for the prespecified noninferiority margin for both criteria). The safety end point, major bleeding, occurred in 15 patients receiving dabigatran (1.2%) and in 22 receiving warfarin (1.7%; hazard ratio, 0.69; 95% CI, 0.36-1.32). Any bleeding occurred in 200 dabigatran (15.6%) and 285 warfarin (22.1%; hazard ratio, 0.67; 95% CI, 0.56-0.81) patients. Deaths, adverse events, and acute coronary syndromes were similar in both groups. Pooled analysis of this study RE-COVER II and the RE-COVER trial gave hazard ratios for recurrent VTE of 1.09 (95% CI, 0.76-1.57), for major bleeding of 0.73 (95% CI, 0.48-1.11), and for any bleeding of 0.70 (95% CI, 0.61-0.79).
Conclusion: Dabigatran has similar effects on VTE recurrence and a lower risk of bleeding compared with warfarin for the treatment of acute VTE.
Clinical trial registration url: www.clinicaltrials.gov. Unique identifiers: NCT00680186 and NCT00291330.
Keywords: antagonists & inhibitors; hemorrhage; recurrence; thrombin; venous thromboembolism; warfarin.
Source: PubMed