Creatinine clearance (CrCl) has been widely used to adjust the dosage of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation (AF) and exclude contraindicated patients. However, there are few available real-world data on the relation between CrCl and adverse clinical outcomes in patients with AF. Therefore, we evaluated the clinical characteristics and adverse events in Japanese patients with AF stratified by CrCl. We categorized patients in the Fushimi AF Registry, a large prospective community-based Japanese cohort of patients with AF, into 3 groups as follows: (1) CrCl <30 ml/min, (2) CrCl 30 to 49 ml/min, and (3) CrCl ≥50 ml/min. We evaluated 3,080 patients after a median follow-up of 1,076 days. Comparing with patients with CrCl ≥50 ml/min, patients with AF with CrCl <30 ml/min showed increased risks of stroke/systemic embolism (SE) (hazard ratio [HR] 1.68; 95% confidence interval [CI] 1.04 to 2.65; p = 0.04) and major bleeding (HR, 2.08; 95% CI 1.23 to 3.39; p = 0.008) after adjustment for prespecified factors. Patients with AF with CrCl <30 ml/min were also associated with higher risks of all-cause death, hospitalization for heart failure, myocardial infarction, or the composite of all-cause death and stroke/SE. However, no excess risk of stroke/SE (HR 1.10; 95% CI 0.76 to 1.58; p = 0.6) or major bleeding (HR 0.98; 95% CI 0.63 to 1.48; p = 0.9) was noted for patients with CrCl 30 to 49 ml/min. In conclusion, Japanese patients with AF with CrCl <30 ml/min were closely associated with adverse clinical events including stroke/SE and major bleeding.
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