Residual Stroke Risk Among Patients With Atrial Fibrillation Prescribed Oral Anticoagulants: A Patient-Level Meta-Analysis From COMBINE AF

• Published in: Journal of the American Heart Association 2024-09, Vol.13 (17), p.e034758
• Main Authors: Johnson, Linda S, Benz, Alexander P, Shoamanesh, Ashkan, Eikelboom, John W, Ezekowitz, Michael, Giugliano, Robert P, Wallentin, Lars, Ruff, Christian T, Lopes, Renato D, Jolly, Sanjit, Whitlock, Richard, Granger, Christopher B, Connolly, Stuart, Healey, Jeffrey S
• Format: Article
• Language: English
• Subjects: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants - administration & dosage; Anticoagulants - adverse effects; anticoagulation; atrial fibrillation; Atrial Fibrillation - complications; Atrial Fibrillation - diagnosis; Atrial Fibrillation - drug therapy; Cardiac and Cardiovascular Systems; Clinical Medicine; Female; Humans; Ischemic Stroke - diagnosis; Ischemic Stroke - epidemiology; Ischemic Stroke - etiology; Ischemic Stroke - prevention & control; JAHA Spotlight: Neurocardiology; Kardiologi; Klinisk medicin; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Middle Aged; Original Research; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; stroke
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/JAHA.123.034758

Despite oral anticoagulation, patients with atrial fibrillation (AF) remain at risk of ischemic stroke and systemic embolism (SE) events. For patients whose residual risk is sufficiently high, additional therapies might be useful to mitigate stroke risk. Individual patient data from 5 landmark trials testing oral anticoagulation in AF were pooled in A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in AF (COMBINE AF). We calculated the rate of ischemic stroke/SE among oral anticoagulation-treated patients with a CHA DS -VASc score≥2, across strata of CHA DS -VASc score, stroke history, and AF type, as either paroxysmal or nonparoxysmal. We included 71 794 patients with AF (median age 72 years, interquartile range, 13 years, 61.3% male) randomized to a direct oral anticoagulant or vitamin K antagonist, and followed for a mean of 2.1 (±0.8) years. The median CHA DS -VASc score was 4 (interquartile range, 3-5), 18.8% had a prior stroke, and 76.4% had nonparoxysmal AF. The overall rate of stroke/SE was 1.33%/y (95% CI, 1.27-1.39); 1.38%/y (95% CI, 1.31-1.45) for nonparoxysmal AF, and 1.15%/y (95% CI, 1.05-1.27) for paroxysmal AF. The rate of ischemic stroke/SE increased by a rate ratio of 1.36 (95% CI, 1.32-1.41) per 1-point increase in CHA DS -VASc, reaching 1.67%/y (95% CI, 1.59-1.75) ≥4 CHA DS -VASc points. Patients with both nonparoxysmal AF and CHA DS -VASc ≥4 had a stroke/SE rate of 1.75%/y (95% CI, 1.66-1.85). In patients with a prior stroke, the risk was 2.51%/y (95% CI, 2.33-2.71). AF type, CHA DS -VASc score, and stroke history can identify patients with AF, who despite oral anticoagulation have a residual stroke/SE risk of 1.5% to 2.5% per year. Evaluation of additional stroke/SE prevention strategies in high-risk patients is warranted.