Impact of creatinine clearance on clinical outcomes in elderly atrial fibrillation patients receiving apixaban: J-ELD AF Registry subanalysis

Background Randomized clinical trials demonstrated the efficacy and safety of apixaban in preventing stroke in patients with atrial fibrillation (AF). However, data on patients with low creatinine clearance (CCr), especially CCr 15-29 mL min, are limited. Methods The J-ELD AF Registry is a large-scale, multicenter prospective observational study of Japanese nonvalvular AF patients aged >= 75 years taking on-label dose (standard dose of 5 mg bid or reduced dose of 2.5 mg bid) of apixaban. The entire cohort (3,015 patients from 110 institutions) was divided into 3 CCr subgroups: CCr >= 50 H./min (n = 1,165, 38.6%), CCr 30-49 ml/min (n = 1,395, 46.3%), and CCr 15-29 ml/min (n = 455, 15.1%). Results The event incidence rates (/100 person-years) were 1.76, 1.39, and 1.67 for stroke or systemic embolism (log rank P = .762); 1.39, 1.93, and 3.13 for bleeding requiring hospitalization (log rank P = .159); 1.75, 2.76, and 7.87 for total deaths (log rank P < .001); and 0.46, 0.84, and 2.62 for cardiovascular deaths (log rank P < .001), respectively. After adjusting for confounders by Cox regression analysis, CCr 15-29 was an independent risk for total death and cardiovascular death but not for stroke or systemic embolism, or bleeding requiring hospitalization. Conclusions The incidence of events in each CCr value group was comparable For stroke or systemic embolism and bleeding requiring hospitalization, and significantly higher for total deaths and cardiovascular deaths only in the CCr 15- to 29-mL/min group, in Japanese nonvalvular AF patients aged >= 75 years.