Previous trials of specific direct oral anticoagulants (DOACs) to prevent cardiovascular events provided conflicting evidence. Trials with rivaroxaban for patients with atherosclerotic cardiovascular disease (ie, ATLAS ACS 2–TIMI 51 and COMPASS) showed that rivaroxaban plus aspirin reduced the risk for a composite of cardiovascular death, stroke, or myocardial infarction but increased the risk for major bleeding compared with aspirin alone.1,2 However, the APPRAISE-2 trial was terminated early because apixaban increased the risk for major bleeding without reduction in recurrent ischemic events in patients after acute coronary syndrome.