Non–Vitamin K Antagonist Oral Anticoagulants in Asian Patients With Supranormal Renal Function

Background and Purpose- In clinical trials, the reduced efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention was reported for patients with nonvalvular atrial fibrillation with a creatinine clearance (CrCl) >95 mL/min compared with that of warfarin. We examined the effectiveness, safety, and net clinical benefit of NOACs compared with warfarin in Asian patients with atrial fibrillation and supranormal renal function. Methods- Using data from the Korean National Health Insurance Service database from January 2014 to December 2016, we included patients with nonvalvular atrial fibrillation with CrCl >80 mL/min. Among these incident oral anticoagulant users with rivaroxaban (n=6297), dabigatran (n=4241), apixaban (n=3395), edoxaban (n=1187), and warfarin (n=9884) were analyzed. Propensity score weighting was used to balance covariates across study groups. Hazard ratios for ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, all-cause death, and the composite outcome defined as ischemic stroke+intracranial hemorrhage+gastrointestinal bleeding+all-cause death were analyzed using Cox regression analysis with warfarin as the reference. Results- Baseline characteristics were well balanced among all groups (mean age, 66±11 years; 63% were men; mean CHA₂DS₂-VASc score, 3.0±1.8). Forty-five percent of the patients had CrCl >95 mL/min. Pooled NOACs yielded lower risks of ischemic stroke (hazard ratio, 0.51; 95% CI, 0.43-0.60) and the composite outcome (hazard ratio, 0.64; 95% CI, 0.58-0.70) than warfarin in patients with CrCl >80 mL/min. These benefits were consistent in those with CrCl >95 mL/min. All 4 NOACs reduced the risks of ischemic stroke and the composite outcome in both patients with CrCl >80 mL/min and >95 mL/min. Conclusions- The NOACs showed better effectiveness and safety than warfarin in the patients with atrial fibrillation and supranormal renal function; this was consistently observed for all 4 NOACs and in patients with CrCl >95 mL/min.