A review of apixaban for stroke prevention in atrial fibrillation: insights from ARISTOTLE

Abstract

Atrial fibrillation (AF) is associated with significant mortality and morbidity, and stroke represents the most-feared complication. Consequently, AF treatment has focused on thromboprophylaxis, with warfarin as the mainstay of therapy. However, concerns over ease of use and safety have limited its use. Three novel oral anticoagulants have been approved for use in stroke prevention in AF based on randomized data: 1) dabigatran, studied in Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY); 2) rivaroxaban, studied in 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); and 3) apixaban, studied inApixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE). In this review, we focus on apixaban and discuss subgroup analyses that have been performed in the three trials comparing novel oral anticoagulants with warfarin. We conclude with recommendations regarding further investigations.

Keywords: :

• atrial fibrillation
• oral anticoagulants
• stroke prevention

Financial & competing interests disclosure

R Lopes is a consultant and serves on the advisory boards for Pfizer/BMS, Boehringer Ingelheim, Bayer and Johnson & Johnson. CB Granger is a consultant for Daiichi and is a consultant and conducts research for Pfizer/BMS and Boehringer Ingelheim. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Warfarin reduces thromboembolic stroke in patients with atrial fibrillation (AF) but significantly increases the risk of major bleeding (particularly intracranial bleeding) and can be difficult to use.

• • Compared with warfarin, dabigatran and rivaroxaban are noninferior and apixaban is superior for prevention of stroke and systemic embolism and reduction of intracranial hemorrhage in AF patients.

• • Apixaban has an appealing profile due to a reduction in mortality, in addition to less stroke and major bleeding compared with warfarin for treatment of AF.

• • In general, it appears that the newer oral anticoagulants provide consistent benefit regardless of patients’ stroke or bleeding risk, history of prior stroke or transient ischemic attack, left ventricular systolic dysfunction, type or duration of AF, degree of moderate renal impairment and time in therapeutic range on warfarin.

• • Further investigation into the performance of these agents in special clinical scenarios and patient populations, such as severe renal impairment including dialysis, cardioversion or AF ablation, temporary interruptions in therapy and in combination with dual antiplatelet therapy, is needed.