New Oral Anticoagulants for Atrial Fibrillation: A Review of Clinical Trials

Background: Warfarin had been the only oral anticoagulant for stroke prevention in patients with atrial fibrillation (AF) for decades. Direct thrombin inhibitors and factor Xa inhibitors are new anticoagulants recently approved for prevention of stroke or systemic embolism in patients with AF. Objective: The aim of this article was to provide a systematic review of recently published clinical data on the direct thrombin inhibitors and factor Xa inhibitors in the management of AF. Methods: A search of the ClinicalTrials.gov registry was conducted using the subject terms dabigatran, rivaroxaban, and apixaban. Each search was limited to clinical trials that included patients with AF. Completed studies with warfarin as the main comparator were identified. From the yielded results, the national clinical trial identifier was inputted in PubMed (1966 November 2011) for a search of published literature. Results: Three Phase III clinical trials reported the efficacy of each agent in patients who have AF and risk factors for stroke or embolic complications. The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study reported dabigatran 150 mg was associated with a lower rate of stroke and systemic embolism, whereas dabigatran 110 mg was associated with a similar rate for such events when compared with warfarin (relative risk = 0.66; 95% confidence interval [CI], 0.53-0.82; P < 0.001; and relative risk = 0.91; 95% CI, 0.74-1.11; P = 0.34, respectively). From the intention-to-treat analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, rivaroxaban was reported to be noninferior to warfarin in reducing stroke or systemic embolism (2.1% vs 2.4% per year; hazard ratio = 0.88; 95% CI, 0.75-1.03; P < 0.001). The Apixaban for Reduction in Stroke and Other Thrombotic Events in Atrial Fibrillation (ARISTOTLE) trial reported that apixaban reduced stroke or systemic embolic events by 21% when compared with warfarin (1.27% vs 1.60% per year, respectively; hazard ratio = 0.79; 95% CI, 0.66-0.95; P < 0.001). All 3 agents were associated with similar bleeding when compared with warfarin. Conclusions: Published data suggest that all 3 agents are at least as efficacious as dose-adjusted warfarin, with similar major bleeding profiles. For patients who are unwilling to adhere to regular coagulation monitoring or whose therapeutic effect using warfarin is not optimal despite adequate monitoring and management, the inhibitors of direct thrombin or factor Xa may provide alternative choices in anticoagulation. (Clin Ther. 2012;34:894-901) (C) 2012 Elsevier HS Journals, Inc. All rights reserved.