Clinical Review & Education
From the Medical Letter on Drugs and Therapeutics
Rethinking Warfarin for Atrial Fibrillation Full-page newspaper advertisements and a series of television commercials have urged patients with atrial fibrillation to “rethink warfarin” in favor of Eliquis (apixaban – Bristol-Myers Squibb). Apixaban is the latest of 3 new oral anticoagulants now competing with warfarin (Coumadin, and others) for the oral anticoagulant market.1
New Oral Anticoagulants vs Warfarin Advantages
Unlike warfarin, the new oral anticoagulants do not require INR monitoring and have no dietary restrictions. Dabigatran (Pradaxa), rivaroxaban (Xarelto), and apixaban all appear to be at least as effective as warfarin in preventing stroke in patients with nonvalvular atrial fibrillation. In clinical trials,2-4 they each caused less intracranial bleeding than warfarin,andapixabancausedlessoverallbleeding,5 butthetrialswereconducted in somewhat different populations and used slightly different definitions of major bleeding. Disadvantages
The 3 new oral anticoagulants are all shorter acting than warfarin, so missed doses could increase the risk of thrombosis. Both
apixaban and dabigatran are taken twice daily. Unlike warfarin, the new oral anticoagulants have no specific antidotes to reverse their therapeutic effect; one study found that use of a prothrombin complex concentrate reversed the anticoagulant effect of rivaroxaban, but not dabigatran.6,7 Monitoring of renal function is recommended for dabigatran and rivaroxaban, and probably would be prudent for apixaban as well. All of the new oral anticoagulants are much more expensive than warfarin.
Conclusion Patients with nonvalvular atrial fibrillation who are taking warfarin and whose INR generally remains within the therapeutic range should probably stay on it. New patients and those who are difficult to maintain in the therapeutic range of INR might benefit from treatment with dabigatran (Pradaxa), rivaroxaban (Xarelto), or apixaban (Eliquis). Of the three, apixaban was the only one shown to cause less overall bleeding than warfarin, but direct comparisons between the new drugs and long-term data on outcomes are lacking.
ARTICLE INFORMATION
REFERENCES
The Medical Letter Editors: Gianna Zuccotti, MD, MPH, Executive Editor; Jean-Marie Pflomm, PharmD, Editor
1. Apixaban (Eliquis): a new oral anticoagulant for atrial fibrillation. Med Lett Drugs Ther. 2013;55(1409):9-10.
Previous Publication: This article was previously published: The Medical Letter. September 30, 2013;55(1426):77. ©The Medical Letter Inc.
2. Connolly SJ, Ezekowitz MD, Yusuf S, et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-1151.
About The Medical Letter: The Medical Letter is a nonprofit organization that publishes biweekly new drug evaluations and treatment recommendations. The Medical Letter does not accept advertisements, gifts, grants, or donations. Financial support comes solely from sales of subscriptions, books, software, continuing education materials, and licenses. http://www.medicalletter.org
3. Patel MR, Mahaffey KW, Garg J, et al; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883-891. 4. Granger CB, Alexander JH, McMurray JJ, et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981-992.
Events in Atrial Fibrillation (ARISTOTLE) Investigators. Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation. Circulation. 2013;127(22):2166-2176. 6. Kcentra: a 4-factor prothrombin complex concentrate for reversal of warfarin anticoagulation. Med Lett Drugs Ther. 2013;55(1420):53-54. 7. Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011;124(14):1573-1579.
5. Wallentin L, Lopes RD, Hanna M, et al; Apixaban for Reduction in Stroke and Other Thromboembolic
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JAMA March 26, 2014 Volume 311, Number 12
Copyright 2014 American Medical Association. All rights reserved.
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From the Medical Letter on Drugs and Therapeutics
Rethinking Warfarin for Atrial Fibrillation Full-page newspaper advertisements and a series of television commercials have urged patients with atrial fibrillation to “rethink warfarin” in favor of Eliquis (apixaban – Bristol-Myers Squibb). Apixaban is the latest of 3 new oral anticoagulants now competing with warfarin (Coumadin, and others) for the oral anticoagulant market.1
New Oral Anticoagulants vs Warfarin Advantages
Unlike warfarin, the new oral anticoagulants do not require INR monitoring and have no dietary restrictions. Dabigatran (Pradaxa), rivaroxaban (Xarelto), and apixaban all appear to be at least as effective as warfarin in preventing stroke in patients with nonvalvular atrial fibrillation. In clinical trials,2-4 they each caused less intracranial bleeding than warfarin,andapixabancausedlessoverallbleeding,5 butthetrialswereconducted in somewhat different populations and used slightly different definitions of major bleeding. Disadvantages
The 3 new oral anticoagulants are all shorter acting than warfarin, so missed doses could increase the risk of thrombosis. Both
apixaban and dabigatran are taken twice daily. Unlike warfarin, the new oral anticoagulants have no specific antidotes to reverse their therapeutic effect; one study found that use of a prothrombin complex concentrate reversed the anticoagulant effect of rivaroxaban, but not dabigatran.6,7 Monitoring of renal function is recommended for dabigatran and rivaroxaban, and probably would be prudent for apixaban as well. All of the new oral anticoagulants are much more expensive than warfarin.
Conclusion Patients with nonvalvular atrial fibrillation who are taking warfarin and whose INR generally remains within the therapeutic range should probably stay on it. New patients and those who are difficult to maintain in the therapeutic range of INR might benefit from treatment with dabigatran (Pradaxa), rivaroxaban (Xarelto), or apixaban (Eliquis). Of the three, apixaban was the only one shown to cause less overall bleeding than warfarin, but direct comparisons between the new drugs and long-term data on outcomes are lacking.
ARTICLE INFORMATION
REFERENCES
The Medical Letter Editors: Gianna Zuccotti, MD, MPH, Executive Editor; Jean-Marie Pflomm, PharmD, Editor
1. Apixaban (Eliquis): a new oral anticoagulant for atrial fibrillation. Med Lett Drugs Ther. 2013;55(1409):9-10.
Previous Publication: This article was previously published: The Medical Letter. September 30, 2013;55(1426):77. ©The Medical Letter Inc.
2. Connolly SJ, Ezekowitz MD, Yusuf S, et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-1151.
About The Medical Letter: The Medical Letter is a nonprofit organization that publishes biweekly new drug evaluations and treatment recommendations. The Medical Letter does not accept advertisements, gifts, grants, or donations. Financial support comes solely from sales of subscriptions, books, software, continuing education materials, and licenses. http://www.medicalletter.org
3. Patel MR, Mahaffey KW, Garg J, et al; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883-891. 4. Granger CB, Alexander JH, McMurray JJ, et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981-992.
Events in Atrial Fibrillation (ARISTOTLE) Investigators. Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation. Circulation. 2013;127(22):2166-2176. 6. Kcentra: a 4-factor prothrombin complex concentrate for reversal of warfarin anticoagulation. Med Lett Drugs Ther. 2013;55(1420):53-54. 7. Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011;124(14):1573-1579.
5. Wallentin L, Lopes RD, Hanna M, et al; Apixaban for Reduction in Stroke and Other Thromboembolic
1246
JAMA March 26, 2014 Volume 311, Number 12
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Rutgers University Libraries User on 06/02/2015
jama.com
