Dabigatran versus warfarin in the treatment of acute venous thromboembolism
Sam Schulman, Clive Kearon, Ajay K Kakkar, Patrick Mismetti, Sebastian Schellong, Henry Eriksson, David Baanstra, Janet Schnee, Samuel Z Goldhaber, RE-COVER Study Group, S Schulman, H Eriksson, S Goldhaber, A Kakkar, C Kearon, P Mismetti, S Schellong, E Minar, D Bergqvist, J Tijssen, M Prins, H Büller, J Otten, M Prins, R Peters, M Mac Gillavry, H Büller, S Pol, A Burroughs, I Gilmore, J Bluguermann, O Carlevaro, L Dipaola, P Gitelman, D Santos, P Schygiel, R Baker, P Blombery, A Gallus, E Gan, H Gibbs, H Salem, M Baghestanian, E Pilger, W Sturm, E Debing, A Gadisseur, P Hainaut, P Verhamme, J-C Wautrecht, M Zicot, J M Annichino Bizzachi, G Araujo, J Dalmo De Araujo, F M Duarte Brandão Panico, Y Nagato, A H Pereira, P Puech Leao, E Ramaciotti, R C Rocha Moreira, J Timi, D Anderson, M Crowther, S Dolan, J Eikelboom, F Spencer, M Game, S Kahn, J Kassis, C Kearon, P Klinke, M Kovacs, A Milot, B Ritchie, M Rodger, S Solymoss, J Villeneuve, E Yeo, P Cervinka, M Homza, P Hrdy, Z Klimsa, P Lang, R Maly, I Oral, P Reichert, J Spinar, P Varejka, J Vladimir, J Brønnum-Schou, S Jensen, S E Jensen, K S Kristensen, H Nielsen, O Wiemann, V Bost, A Buchmuller, K Guillot, P Laurent, F Lecomte, D Mottier, I Quere, D Wahl, J Beyer, A Dormann, U Hoffmann, M Maier, A Mietaschk, S Schellong, K Katsenis, C Klonaris, C Liappis, G Acsady, I Berhes, Z Boda, K Farkas, J Jakucs, L Kollar, L Matyas, M Riba, M Sereg, R Aggarwal, D Banker, A Bharani, M Gadkari, J Hiremath, A Jain, S Kareem, S Lyengar, R Parakh, N Sekar, A Srinivas, K Suresh, T Vujay, B Brenner, S Efrati, M Elias, D Gavish, E Grossman, M Lahav, M Lishner, D Zeltser, G Agnelli, C Cimminiello, G Palareti, P Prandoni, M Santonastaso, M Silingardi, E Aldrett Lee, J M Fontes Andrade, J Jaurrieta Valles, D Biesma, A Dees, R Fijnheer, K Hamulyak, M H H Kramer, F W G Leebeek, L Lieverse, M T Nurmohamed, S Chunilal, S Jackson, P Ockelford, M Smith, A M Njaastad, P M Sandseth, A Tveit, A Waage, J Barata, M Capitao, F E Fernandes, A Leitão, L Providência, D I Alohin, S Belentsov, M Chernyatina, A Chernyavsky, A Fokin, A Gubenko, V Alexander V Guz, I Katelnitsky, I Katelnitsky, A A A Khamitov, A Khitaryan, G Khubulava, I Mikhailov, V Shkurin, I Staroverov, A Tchumakov, A Zaporozhsky, T Duris, P Poliacik, V Spisak, M Szentivanyi, V Zubek, D Adler, D Kelbe, D Le Roux, A Pieterse, R Routier, R Siebert, B Sloane, C Smith, H Van Rensburg, J Del Toro, M J García-Fuster, J Mateo, M Monreal, J A Nieto, P Sánchez-Molini, C Sedano, J Trujillo, R Valle, J Villalta, J Aagesen, A Carlsson, H Eriksson, L Johansson, G Lärfars, P Lindmarker, U Säfvenberg, A Själander, U Bengisun, T Calkavur, M R Guney, S Karahan, M Kurtoglu, U Sakinci, A Gubka, V Mishalov, O Skupyy, A Cohen, D Keeling, P Kesteven, P MacCallum, R Maclean, P Shah, H Watson, A Bartkowiak, E Bolster, W C Botnick, B Burnett, A Chervu, A J Comerota, N M Dy, F A Fulco, J R Gossage, S Kaatz, B Lahiri, R G Lerner, J A Masson, S Moll, M Morganroth, K Patel, R Paulson, R Powell, R Samson, A Seibert, A Spyropoulos, P S Vrooman Jr, Sam Schulman, Clive Kearon, Ajay K Kakkar, Patrick Mismetti, Sebastian Schellong, Henry Eriksson, David Baanstra, Janet Schnee, Samuel Z Goldhaber, RE-COVER Study Group, S Schulman, H Eriksson, S Goldhaber, A Kakkar, C Kearon, P Mismetti, S Schellong, E Minar, D Bergqvist, J Tijssen, M Prins, H Büller, J Otten, M Prins, R Peters, M Mac Gillavry, H Büller, S Pol, A Burroughs, I Gilmore, J Bluguermann, O Carlevaro, L Dipaola, P Gitelman, D Santos, P Schygiel, R Baker, P Blombery, A Gallus, E Gan, H Gibbs, H Salem, M Baghestanian, E Pilger, W Sturm, E Debing, A Gadisseur, P Hainaut, P Verhamme, J-C Wautrecht, M Zicot, J M Annichino Bizzachi, G Araujo, J Dalmo De Araujo, F M Duarte Brandão Panico, Y Nagato, A H Pereira, P Puech Leao, E Ramaciotti, R C Rocha Moreira, J Timi, D Anderson, M Crowther, S Dolan, J Eikelboom, F Spencer, M Game, S Kahn, J Kassis, C Kearon, P Klinke, M Kovacs, A Milot, B Ritchie, M Rodger, S Solymoss, J Villeneuve, E Yeo, P Cervinka, M Homza, P Hrdy, Z Klimsa, P Lang, R Maly, I Oral, P Reichert, J Spinar, P Varejka, J Vladimir, J Brønnum-Schou, S Jensen, S E Jensen, K S Kristensen, H Nielsen, O Wiemann, V Bost, A Buchmuller, K Guillot, P Laurent, F Lecomte, D Mottier, I Quere, D Wahl, J Beyer, A Dormann, U Hoffmann, M Maier, A Mietaschk, S Schellong, K Katsenis, C Klonaris, C Liappis, G Acsady, I Berhes, Z Boda, K Farkas, J Jakucs, L Kollar, L Matyas, M Riba, M Sereg, R Aggarwal, D Banker, A Bharani, M Gadkari, J Hiremath, A Jain, S Kareem, S Lyengar, R Parakh, N Sekar, A Srinivas, K Suresh, T Vujay, B Brenner, S Efrati, M Elias, D Gavish, E Grossman, M Lahav, M Lishner, D Zeltser, G Agnelli, C Cimminiello, G Palareti, P Prandoni, M Santonastaso, M Silingardi, E Aldrett Lee, J M Fontes Andrade, J Jaurrieta Valles, D Biesma, A Dees, R Fijnheer, K Hamulyak, M H H Kramer, F W G Leebeek, L Lieverse, M T Nurmohamed, S Chunilal, S Jackson, P Ockelford, M Smith, A M Njaastad, P M Sandseth, A Tveit, A Waage, J Barata, M Capitao, F E Fernandes, A Leitão, L Providência, D I Alohin, S Belentsov, M Chernyatina, A Chernyavsky, A Fokin, A Gubenko, V Alexander V Guz, I Katelnitsky, I Katelnitsky, A A A Khamitov, A Khitaryan, G Khubulava, I Mikhailov, V Shkurin, I Staroverov, A Tchumakov, A Zaporozhsky, T Duris, P Poliacik, V Spisak, M Szentivanyi, V Zubek, D Adler, D Kelbe, D Le Roux, A Pieterse, R Routier, R Siebert, B Sloane, C Smith, H Van Rensburg, J Del Toro, M J García-Fuster, J Mateo, M Monreal, J A Nieto, P Sánchez-Molini, C Sedano, J Trujillo, R Valle, J Villalta, J Aagesen, A Carlsson, H Eriksson, L Johansson, G Lärfars, P Lindmarker, U Säfvenberg, A Själander, U Bengisun, T Calkavur, M R Guney, S Karahan, M Kurtoglu, U Sakinci, A Gubka, V Mishalov, O Skupyy, A Cohen, D Keeling, P Kesteven, P MacCallum, R Maclean, P Shah, H Watson, A Bartkowiak, E Bolster, W C Botnick, B Burnett, A Chervu, A J Comerota, N M Dy, F A Fulco, J R Gossage, S Kaatz, B Lahiri, R G Lerner, J A Masson, S Moll, M Morganroth, K Patel, R Paulson, R Powell, R Samson, A Seibert, A Spyropoulos, P S Vrooman Jr
Abstract
Background: The direct oral thrombin inhibitor dabigatran has a predictable anticoagulant effect and may be an alternative therapy to warfarin for patients who have acute venous thromboembolism.
Methods: In a randomized, double-blind, noninferiority trial involving patients with acute venous thromboembolism who were initially given parenteral anticoagulation therapy for a median of 9 days (interquartile range, 8 to 11), we compared oral dabigatran, administered at a dose of 150 mg twice daily, with warfarin that was dose-adjusted to achieve an international normalized ratio of 2.0 to 3.0. The primary outcome was the 6-month incidence of recurrent symptomatic, objectively confirmed venous thromboembolism and related deaths. Safety end points included bleeding events, acute coronary syndromes, other adverse events, and results of liver-function tests.
Results: A total of 30 of the 1274 patients randomly assigned to receive dabigatran (2.4%), as compared with 27 of the 1265 patients randomly assigned to warfarin (2.1%), had recurrent venous thromboembolism; the difference in risk was 0.4 percentage points (95% confidence interval [CI], -0.8 to 1.5; P<0.001 for the prespecified noninferiority margin). The hazard ratio with dabigatran was 1.10 (95% CI, 0.65 to 1.84). Major bleeding episodes occurred in 20 patients assigned to dabigatran (1.6%) and in 24 patients assigned to warfarin (1.9%) (hazard ratio with dabigatran, 0.82; 95% CI, 0.45 to 1.48), and episodes of any bleeding were observed in 205 patients assigned to dabigatran (16.1%) and 277 patients assigned to warfarin (21.9%; hazard ratio with dabigatran, 0.71; 95% CI, 0.59 to 0.85). The numbers of deaths, acute coronary syndromes, and abnormal liver-function tests were similar in the two groups. Adverse events leading to discontinuation of the study drug occurred in 9.0% of patients assigned to dabigatran and in 6.8% of patients assigned to warfarin (P=0.05).
Conclusions: For the treatment of acute venous thromboembolism, a fixed dose of dabigatran is as effective as warfarin, has a safety profile that is similar to that of warfarin, and does not require laboratory monitoring. (ClinicalTrials.gov number, NCT00291330.)
Copyright 2009 Massachusetts Medical Society.
Source: PubMed