Polypharmacy can affect the safety and efficacy of warfarin, given the many known interactions between warfarin and other drugs. However, the effect of polypharmacy on outcomes with direct oral anticoagulants is unclear. In the ARISTOTLE randomized trial, in which 18,000 people with atrial fibrillation (AF) received apixaban (Eliquis) or warfarin, apixaban was superior to warfarin in preventing stroke or systemic embolism and major bleeding and was associated with …