Relation of Stroke and Major Bleeding to Creatinine Clearance in Patients With Atrial Fibrillation (from the Fushimi AF Registry)

Creatinine clearance (CrCl) has been widely used to adjust the dosage of non-vitamin K antagonist oral anticoagulants in atrial fibrillation (AF) patients and exclude contraindicated patients. However, there are few available real-world data on the relationship between CrCl and adverse clinical outcomes in AF patients. Therefore, we evaluated the clinical characteristics and adverse events in Japanese AF patients stratified by CrCl. We categorized patients in the Fushimi AF Registry, a large prospective community-based Japanese cohort of AF patients, into three groups as follows: (i) CrCl<30 mL/min, (ii) CrCl 30-49 mL/min, and (iii) 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, AF patients 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 pre-specified factors. AF patients 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 30-49 mL/min. In conclusion, Japanese AF patients with CrCl <30 mL/min were closely associated with adverse clinical events including stroke/SE and major bleeding.