Systemic Embolic Events in Atrial Fibrillation: An Individual Patient Data Meta-analysis of 71 683 Participants Randomized to NOAC Versus Warfarin

BACKGROUND: Systemic embolic events (SEEs) are a serious but underrecognized complication of atrial fibrillation. Although non–vitamin K antagonist oral anticoagulants prevent ischemic stroke (IS), their efficacy in SEE and the clinical characteristics of patients who experience SEE remain poorly understood. METHODS: We analyzed individual patient data from 4 pivotal randomized trials enrolling patients between 2005 and 2010 comparing non–vitamin K antagonist oral anticoagulants versus warfarin in atrial fibrillation. We characterized the incidence, clinical features, management, and outcomes of clinically overt SEE and compared results in these patients with patients who had an IS. RESULTS: Among 71 683 patients, 188 experienced SEE (26 with concurrent IS), yielding an annualized event rate of 0.13% per patient-year, compared with 1.25% per patient-year for IS (n=1797). Among 171 patients with SEE as their first event, median age was 75 years (interquartile range, 68–80), 49.7% were female, and mean±SD CHA 2 DS 2 -VASc score was 4. 7 ±1.5. Compared with IS, patients with SEE had higher rates of peripheral arterial disease (PAD, 16.5% versus 5.4%; P