Apixaban versus warfarin in patients with atrial fibrillation.

Abstract

BACKGROUND:

Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin.

METHODS:

In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause.

RESULTS:

The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P=0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P=0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P=0.42).

CONCLUSIONS:

In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. (Funded by Bristol-Myers Squibb and Pfizer; ARISTOTLE ClinicalTrials.gov number, NCT00412984.).

• Authors: Christopher B Granger, John H Alexander, John J V McMurray, Renato D Lopes, Elaine M Hylek, Michael Hanna, Hussein R Al-Khalidi, Jack Ansell, Dan Atar, Alvaro Avezum, M Cecilia Bahit, Rafael Diaz, J Donald Easton, Justin A Ezekowitz, Greg Flaker, David Garcia, Margarida Geraldes, Bernard J Gersh, Sergey Golitsyn, Shinya Goto, Antonio G Hermosillo, Stefan H Hohnloser, John Horowitz, Puneet Mohan, Petr Jansky, Basil S Lewis, Jose Luis Lopez-Sendon, Prem Pais, Alexander Parkhomenko, Freek W A Verheugt, Jun Zhu, Lars Wallentin, ARISTOTLE Committees and Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 365 Issue 11 Pg. 981-92 (Sep 15 2011) ISSN: 1533-4406 [Electronic] United States
• PMID: 21870978 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Factor Xa Inhibitors
• Pyrazoles
• Pyridones
• apixaban
• Warfarin

Topics

• Aged
• Anticoagulants (adverse effects, therapeutic use)
• Atrial Fibrillation (complications, drug therapy)
• Double-Blind Method
• Factor Xa Inhibitors
• Female
• Follow-Up Studies
• Hemorrhage (chemically induced)
• Humans
• International Normalized Ratio
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Pyrazoles (adverse effects, therapeutic use)
• Pyridones (adverse effects, therapeutic use)
• Stroke (prevention & control)
• Thromboembolism (prevention & control)
• Treatment Outcome
• Warfarin (adverse effects, therapeutic use)