Comparing Direct Oral Anticoagulants and Warfarin for Atrial Fibrillation, Venous Thromboembolism, and Mechanical Heart Valves

OBJECTIVES: To summarize available data for use of direct oral anticoagulants in nonvalvular atrial fibrillation, venous thromboembolism, and mechanical heart valves including dose-response consistency to offer considerations for pharmacotherapeutic decision-making for oral anticoagulants. DATA SOURCES: A Medline search of English-language studies published between 2000 and March 2015 was conducted to identify pertinent papers using combinations of the following words: apixaban, atrial fibrillation, dabigatran, direct oral anticoagulant, edoxaban, factor IIa inhibitors, factor Xa inhibitors, mechanical heart valves, novel oral anticoagulant, rivaroxaban, venous thromboembolism, and warfarin. STUDY SELECTION AND EXTRACTION: Original studies, guidelines, and approved prescribing information were evaluated and included if contributing new or complementary data toward the objective. References for all identified studies were reviewed and entries included if contributory. DATA SYNTHESIS: Randomized controlled trials have established the safety and efficacy of direct oral anticoagulants in atrial fibrillation and venous thromboembolism for most patient groups. Direct oral anticoagulants should not be used in patients with mechanical heart valves until proven safe and effective. There are groups for which questions remain regarding inter-patient dose-response consistency for direct oral anticoagulants. There are postmarketing data suggesting poorer real-world performance of dabigatran relative to clinical trial data. CONCLUSION: Direct oral anticoagulants offer several advantages over warfarin, and large clinical trial data establish the appropriateness of their use in broad populations. There remain groups for whom the relative benefit and risk of these agents relative to warfarin are uncertain. A patient-specific approach in pharmacotherapeutic decision-making is appropriate.