Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism
Jeffrey I Weitz, Anthonie W A Lensing, Martin H Prins, Rupert Bauersachs, Jan Beyer-Westendorf, Henri Bounameaux, Timothy A Brighton, Alexander T Cohen, Bruce L Davidson, Hervé Decousus, Maria C S Freitas, Gerlind Holberg, Ajay K Kakkar, Lloyd Haskell, Bonno van Bellen, Akos F Pap, Scott D Berkowitz, Peter Verhamme, Philip S Wells, Paolo Prandoni, EINSTEIN CHOICE Investigators, Alessandra Bianchi, Tim Brighton, Patrick Carroll, Beng Chong, Sanjeev Chunilal, Paul Coughlin, Jennifer Curnow, David Jackson, Huyen Tran, Chris Ward, Marianne Brodmann, Paul Kyrle, Peter Marschang, Ventzislav Petkov, Philippe Hainaut, Paul Jordens, Jos Vandekerkhof, Peter Verhamme, Jean-Claude Wautrecht, Joyce Annichino-Bizzacchi, Bonno van Bellen, Joao Correa, Alberto Cukier, Antonio Freire, Adamastor Pereira, Carmen Porto, Roberto Sacilotto, Agenor Vasconcelos Costa, Anthony Della Siega, Sean Dolan, Grégoire Le Gal, Peter Gross, Susan Kahn, Jeannine Kassis, Michael Kovacs, Yves Pesant, Bruce Ritchie, Sam Schulman, Sudeep Shivakumar, Susan Solymoss, Shu Chang, Rongchang Chen, Zhong Chen, Hong Chen, Xiangchen Dai, Baoming Fang, Weiguo Fu, Xinglin Gao, Jinhua Huang, Yanping Lai, Li Li, Xiaoqiang Li, Yiqing Li, Jinming Liu, Shuang Liu, Wenjiang Ma, Songshi Ni, Zhiqiang Qin, Guochao Shi, Hongyan Tian, Shenming Wang, Lie Wang, Wei Xiao, Kejing Ying, Guanfeng Yu, Yadong Yuan, Jie Zhang, Jin Zhang, Xinri Zhang, Liyan Zhang, Lei Zhu, Jaromir Chlumský, Jiri Chochola, Milna Dunaj, Katerina Kovarova, Pavel Lang, Petr Matoška, Ivo Podpera, Rudolf Spacek, Olga Stehlikova, Jens Brønnum-Schou, Kenneth Egstrup, Gunnar Gislason, Jorgen Jeppesen, Ole May, Henrik Nielsen, Henrik Wiggers, Antoine Achkar, Sandro Aquilanti, Ygal Benhamou, Dominique Brisot, Alessandra Bura-Riviere, Nadine Castella, Antoine Elias, Nicolas Falvo, Emile Ferrari, Philippe Lacroix, Isabelle Mahe, Nicolas Meneveau, Emmanuel Messas, Patrick Mismetti, Karine Montaclair, Dominique Mottier, Thomas Moumneh, Nicolas Paleiron, Florence Parent, Gilles Pernod, Olivier Sanchez, Jeannot Schmidt, Guy Simoneau, Dominique Stephan, Berthold Amann, Rupert Bauersachs, Jan Beyer-Westendorf, Erwin Blessing, Michael Czihal, Christine Espinola-Klein, Gerd Kahrmann, Manuela Licka, Axel Neumeister, Sebastian Schellong, Zoltan Boda, Katalin Farkas, Mihaly Gurzo, Andras Katona, Maria Riba, Gyula Sipos, Kalman Tóth, Andrei Braester, Mazen Elias, Anat Gafter-Gvili, Dov Gavish, Osamah Hussein, Michael Lishner, Elad Schiff, Galia Spectre, Inna Tzoran-Rozenthal, Reuven Zimlichman, Walter Ageno, Giancarlo Agnelli, Carlo Bova, Raffaella Garbelotto, Angelo Ghirarduzzi, Davide Imberti, Raffaele Pesavento, Ettore Porreca, Adriana Visonà, Luis Flota Cervera, Guillermo Llamas Esperón, Daniel Rodriguez-Gonzalez, Lucas Solis Morales, Willem Boersma, Hugo ten Cate, Franciscus Erdkamp, Anita Grifioen-Keijzer, Marinus Marwijk Kooy, Karina Meijer, Saskia Middeldorp, Janneke Swart-Heikens, Marije Ten Wolde, Peter Westerweel, Irene Braithwaite, Paul Harper, Eileen Merriman, Paul Ockelford, Gordon Royle, Mark Smith, Waleed Ghanima, Per Morten Sandset, Maria Abola, Pawel Chęciński, Pawel Grzelakowski, Jerzy Lewczuk, Bozena Sobkowicz, Witold Tomkowski, Igor Abramov, Pavel Chechulov, Andrey Karpenko, Ivan Katelnitskiy, Andrey Kazakov, Olga Makarova, Elizaveta Panchenko, Elena Sergeeva, Yuriy Subbotin, Igor Suchkov, Mikhail Zeltser, David Adler, Johannes Breedt, Nyda Fourie, Rashid Isaacs, Barry Jacobson, Heidi Siebert, Louis van Zyl, Jung-Hyun Choi, Seok-Min Kang, Kye-Hun Kim, Hyo-Soo Kim, Dong-Ik Kim, Seung-Kee Min, Ki Hyuk Park, Fernando García-Bragado Dalmau, Jorge Gómez Cerezo, Jose Carlos Ferrer Mirete, Antonio Riera, Jorge Del Toro, Henry Eriksson, Ingemar Torstensson, Martin Banyai, Iris Baumgartner, Lucia Mazzolai, Daniel Periard, Marc Righini, Daniel Staub, Chern-En Chiang, Kuan-Ming Chiu, Pei-Ying Pai, Pantep Angchaisuksiri, Kanchana Chansung, Gul Öngen, Esin Tuncay, Raza Alikhan, Ian Chetter, Patrick Kesteven, Tim Nokes, Kenneth Bauer, Anthony Comerota, Darlene Elias, David Garcia, Kathleen Gibson, Daniel Ginsberg, Jeffrey Jenkins, Edwin Kingsley, Richard Lambert, Roger Lyons, John Pullman, Vinay Shah, S Wayne Smith, Robert Stein, Victor Tapson, John Walsh, Tzu-Fei Wang, Doan Do Loi, Huan Do Quang, Nguyen Pham, Jeffrey I Weitz, Anthonie W A Lensing, Martin H Prins, Rupert Bauersachs, Jan Beyer-Westendorf, Henri Bounameaux, Timothy A Brighton, Alexander T Cohen, Bruce L Davidson, Hervé Decousus, Maria C S Freitas, Gerlind Holberg, Ajay K Kakkar, Lloyd Haskell, Bonno van Bellen, Akos F Pap, Scott D Berkowitz, Peter Verhamme, Philip S Wells, Paolo Prandoni, EINSTEIN CHOICE Investigators, Alessandra Bianchi, Tim Brighton, Patrick Carroll, Beng Chong, Sanjeev Chunilal, Paul Coughlin, Jennifer Curnow, David Jackson, Huyen Tran, Chris Ward, Marianne Brodmann, Paul Kyrle, Peter Marschang, Ventzislav Petkov, Philippe Hainaut, Paul Jordens, Jos Vandekerkhof, Peter Verhamme, Jean-Claude Wautrecht, Joyce Annichino-Bizzacchi, Bonno van Bellen, Joao Correa, Alberto Cukier, Antonio Freire, Adamastor Pereira, Carmen Porto, Roberto Sacilotto, Agenor Vasconcelos Costa, Anthony Della Siega, Sean Dolan, Grégoire Le Gal, Peter Gross, Susan Kahn, Jeannine Kassis, Michael Kovacs, Yves Pesant, Bruce Ritchie, Sam Schulman, Sudeep Shivakumar, Susan Solymoss, Shu Chang, Rongchang Chen, Zhong Chen, Hong Chen, Xiangchen Dai, Baoming Fang, Weiguo Fu, Xinglin Gao, Jinhua Huang, Yanping Lai, Li Li, Xiaoqiang Li, Yiqing Li, Jinming Liu, Shuang Liu, Wenjiang Ma, Songshi Ni, Zhiqiang Qin, Guochao Shi, Hongyan Tian, Shenming Wang, Lie Wang, Wei Xiao, Kejing Ying, Guanfeng Yu, Yadong Yuan, Jie Zhang, Jin Zhang, Xinri Zhang, Liyan Zhang, Lei Zhu, Jaromir Chlumský, Jiri Chochola, Milna Dunaj, Katerina Kovarova, Pavel Lang, Petr Matoška, Ivo Podpera, Rudolf Spacek, Olga Stehlikova, Jens Brønnum-Schou, Kenneth Egstrup, Gunnar Gislason, Jorgen Jeppesen, Ole May, Henrik Nielsen, Henrik Wiggers, Antoine Achkar, Sandro Aquilanti, Ygal Benhamou, Dominique Brisot, Alessandra Bura-Riviere, Nadine Castella, Antoine Elias, Nicolas Falvo, Emile Ferrari, Philippe Lacroix, Isabelle Mahe, Nicolas Meneveau, Emmanuel Messas, Patrick Mismetti, Karine Montaclair, Dominique Mottier, Thomas Moumneh, Nicolas Paleiron, Florence Parent, Gilles Pernod, Olivier Sanchez, Jeannot Schmidt, Guy Simoneau, Dominique Stephan, Berthold Amann, Rupert Bauersachs, Jan Beyer-Westendorf, Erwin Blessing, Michael Czihal, Christine Espinola-Klein, Gerd Kahrmann, Manuela Licka, Axel Neumeister, Sebastian Schellong, Zoltan Boda, Katalin Farkas, Mihaly Gurzo, Andras Katona, Maria Riba, Gyula Sipos, Kalman Tóth, Andrei Braester, Mazen Elias, Anat Gafter-Gvili, Dov Gavish, Osamah Hussein, Michael Lishner, Elad Schiff, Galia Spectre, Inna Tzoran-Rozenthal, Reuven Zimlichman, Walter Ageno, Giancarlo Agnelli, Carlo Bova, Raffaella Garbelotto, Angelo Ghirarduzzi, Davide Imberti, Raffaele Pesavento, Ettore Porreca, Adriana Visonà, Luis Flota Cervera, Guillermo Llamas Esperón, Daniel Rodriguez-Gonzalez, Lucas Solis Morales, Willem Boersma, Hugo ten Cate, Franciscus Erdkamp, Anita Grifioen-Keijzer, Marinus Marwijk Kooy, Karina Meijer, Saskia Middeldorp, Janneke Swart-Heikens, Marije Ten Wolde, Peter Westerweel, Irene Braithwaite, Paul Harper, Eileen Merriman, Paul Ockelford, Gordon Royle, Mark Smith, Waleed Ghanima, Per Morten Sandset, Maria Abola, Pawel Chęciński, Pawel Grzelakowski, Jerzy Lewczuk, Bozena Sobkowicz, Witold Tomkowski, Igor Abramov, Pavel Chechulov, Andrey Karpenko, Ivan Katelnitskiy, Andrey Kazakov, Olga Makarova, Elizaveta Panchenko, Elena Sergeeva, Yuriy Subbotin, Igor Suchkov, Mikhail Zeltser, David Adler, Johannes Breedt, Nyda Fourie, Rashid Isaacs, Barry Jacobson, Heidi Siebert, Louis van Zyl, Jung-Hyun Choi, Seok-Min Kang, Kye-Hun Kim, Hyo-Soo Kim, Dong-Ik Kim, Seung-Kee Min, Ki Hyuk Park, Fernando García-Bragado Dalmau, Jorge Gómez Cerezo, Jose Carlos Ferrer Mirete, Antonio Riera, Jorge Del Toro, Henry Eriksson, Ingemar Torstensson, Martin Banyai, Iris Baumgartner, Lucia Mazzolai, Daniel Periard, Marc Righini, Daniel Staub, Chern-En Chiang, Kuan-Ming Chiu, Pei-Ying Pai, Pantep Angchaisuksiri, Kanchana Chansung, Gul Öngen, Esin Tuncay, Raza Alikhan, Ian Chetter, Patrick Kesteven, Tim Nokes, Kenneth Bauer, Anthony Comerota, Darlene Elias, David Garcia, Kathleen Gibson, Daniel Ginsberg, Jeffrey Jenkins, Edwin Kingsley, Richard Lambert, Roger Lyons, John Pullman, Vinay Shah, S Wayne Smith, Robert Stein, Victor Tapson, John Walsh, Tzu-Fei Wang, Doan Do Loi, Huan Do Quang, Nguyen Pham
Abstract
Background: Although many patients with venous thromboembolism require extended treatment, it is uncertain whether it is better to use full- or lower-intensity anticoagulation therapy or aspirin.
Methods: In this randomized, double-blind, phase 3 study, we assigned 3396 patients with venous thromboembolism to receive either once-daily rivaroxaban (at doses of 20 mg or 10 mg) or 100 mg of aspirin. All the study patients had completed 6 to 12 months of anticoagulation therapy and were in equipoise regarding the need for continued anticoagulation. Study drugs were administered for up to 12 months. The primary efficacy outcome was symptomatic recurrent fatal or nonfatal venous thromboembolism, and the principal safety outcome was major bleeding.
Results: A total of 3365 patients were included in the intention-to-treat analyses (median treatment duration, 351 days). The primary efficacy outcome occurred in 17 of 1107 patients (1.5%) receiving 20 mg of rivaroxaban and in 13 of 1127 patients (1.2%) receiving 10 mg of rivaroxaban, as compared with 50 of 1131 patients (4.4%) receiving aspirin (hazard ratio for 20 mg of rivaroxaban vs. aspirin, 0.34; 95% confidence interval [CI], 0.20 to 0.59; hazard ratio for 10 mg of rivaroxaban vs. aspirin, 0.26; 95% CI, 0.14 to 0.47; P<0.001 for both comparisons). Rates of major bleeding were 0.5% in the group receiving 20 mg of rivaroxaban, 0.4% in the group receiving 10 mg of rivaroxaban, and 0.3% in the aspirin group; the rates of clinically relevant nonmajor bleeding were 2.7%, 2.0%, and 1.8%, respectively. The incidence of adverse events was similar in all three groups.
Conclusions: Among patients with venous thromboembolism in equipoise for continued anticoagulation, the risk of a recurrent event was significantly lower with rivaroxaban at either a treatment dose (20 mg) or a prophylactic dose (10 mg) than with aspirin, without a significant increase in bleeding rates. (Funded by Bayer Pharmaceuticals; EINSTEIN CHOICE ClinicalTrials.gov number, NCT02064439 .).
Source: PubMed