Apixaban for Stroke Prevention in Atrial Fibrillation: A Review of the Clinical Trial Evidence

The objective of this review is to summarize data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) and Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) trials of apixaban for stroke prevention in patients with atrial fibrillation (AF). The ARISTOTLE trial compared apixaban with warfarin in 18 201 patients with AF and ≥ 1 additional risk factor for stroke. The AVERROES trial compared apixaban with aspirin in 5599 patients with AF who were at increased risk of stroke and for whom vitamin K antagonists were unsuitable. In ARISTOTLE, apixaban reduced the risk of stroke or systemic embolism by 21% compared with warfarin (1.27% vs 1.60% per year; hazard ratio, 0.79; 95% confidence interval, 0.66-0.95). The reduction was significant and demonstrated the superiority of apixaban over warfarin for the primary outcome of preventing stroke or systemic embolism (P = 0.01 for superiority). Apixaban also reduced all-cause mortality by 11% (P = 0.047) and major bleeding by 31% (P < 0.001) compared with warfarin. The benefits of apixaban observed in ARISTOTLE are further supported by the results from AVERROES, which demonstrated a 55% reduction in the risk of stroke or systemic embolism compared with aspirin. Risk of major bleeding was not significantly different between apixaban and aspirin. Subgroup analyses in both trials demonstrated that the effects of apixaban are highly consistent across various patient subpopulations. Discontinuation of study medication was significantly lower with apixaban than with either warfarin in ARISTOTLE or aspirin in AVERROES. Apixaban is the first new oral anticoagulant that has been shown to be superior to warfarin in reducing stroke or systemic embolism, all-cause mortality, and major bleeding in patients with AF. Moreover, in patients with AF who are considered unsuitable for warfarin therapy, apixaban was more effective than aspirin for stroke prevention and had a similar rate of major bleeding.