Abstract 14628: Residual Stroke Risk Among Atrial Fibrillation Patients Treated With Warfarin or Novel Oral Anticoagulants: A Patient Level Meta-Analysis From Combine AF

Introduction: Despite oral anticoagulation treatment atrial fibrillation (AF) patients have residual risk of ischemic stroke and systemic embolism (SE) which could potentially be mitigated. Methods: Harmonized individual patient data from five landmark trials testing direct oral anticoagulants (DOAC) were pooled in the COMBINE-AF dataset, which we used to calculate annual rate of ischemic stroke/SE according to CHA 2 DS 2 -Vasc score, history of stroke, and AF type. Results: We included 71,794 subjects (median age 72 IQR 65-78 years 61.3% male) with CHA 2 DS 2 -Vasc scores≥2 randomized to either standard- or lower-dose DOAC or warfarin, and followed for a median of 2.1 (IQR 1.5-2.7) years. The median CHA 2 DS 2 -VASc score was 4 (IQR 3-5), and 18.8% had a history of stroke and 76.4% had non-paroxysmal AF. The overall annual stroke/SE rate was 1.33%/year (95%CI 1.27-1.39%). Subjects with non-paroxysmal AF had higher stroke/SE rates, 1.38%/year (95%CI 1.31-1.45%) compared to 1.15%/year (95%CI 1.05-1.27%) with paroxysmal AF. The rate increased by a RR 1.36 (95%CI 1.32-1.41%) per CHA 2 DS 2 -VASc point; in subjects with CHA 2 DS 2 -VASc≥4, the stroke/SE rate was 1.67%/year (95%CI 1.59-1.75%). Annual stroke/SE rates were higher in subjects with a prior stroke, 2.51%/year (95%CI 2.33-2.71%), and increased with higher CHA 2 DS 2 -VaSc score; RR 1.11 (95%CI 1.05-1.18), Figure 1 . After premature permanent discontinuation of study drug, which occurred in 22% of individuals, stroke/SE rates were 3.6%/year (95%CI 3.4-3.9%) overall; 6.5%/year (95%CI 5.7-7.4%) in those with prior stroke. During follow-up 8.9% of subjects died. Conclusions: Despite treatment with oral anticoagulation in a clinical trial setting, there remains an 8.4% risk of stroke/SE over five years in subjects with CHA 2 DS 2 -Vasc≥4, and 12.5% over five years in subjects with a prior stroke. Permanent discontinuation is common, and associated with stroke/SE risks of almost 20% over five years.