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

Abstract

Abstract 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 non-valvular 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 enrollment period was from September 2015 to August 2016, and the observation period for each patient was 1 year. The entire cohort (3,015 patients from 110 institutions) was divided into three CCr subgroups: CCr ≥50 mL/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 Most patients (74.3%) in the CCr ≥50 group received the standard apixaban dose, and most (97.4%) in the CCr 15–29 group received the reduced apixaban dose. The average age was 79.2 years for the CCr ≥50 group, 82.5 years for the CCr 30–49 group, and 85.6 years for the CCr 15–29 group. The lower CCr value group included more female patients, had lower body weight, and less cases of paroxysmal AF, as well as more cases of heart failure, peripheral artery disease, and myocardial infarction as comorbidities. The CHA2DS2-VASc and HAS-BLED scores were 4.2±1.2 and 2.4±0.8 for the CCr ≥50 group, 4.5±1.2 and 2.4±0.8 for the CCr 30–49 group, and 4.9±1.2 and 2.4±0.7 for the CCr 15–29 group, respectively. Kaplan Meier curves for cumulative incidence of events are shown in Figure. The event incidence rates (/100 person-years) were 1.76, 1.39, and 1.67 for stroke or systemic embolism (log rank p=0.762), 1.39, 1.93, and 3.13 for bleeding requiring hospitalization (log rank p=0.159), 1.75, 2.76, and 7.87 for total deaths (log rank p<0.001), and 0.46, 0.84, and 2.62 for cardiovascular deaths (log rank p<0.001), in the CCr ≥50 group, CCr 30–49 group, and CCr 15–29 group, respectively. After adjusting for confounders by Cox regression analysis, CCr 15–29 was an independent risk for total death [hazard ratio (HR) 3.22, 95% confidence interval (CI) 1.68–6.17, with reference to the CCr ≥50 group] and cardiovascular death [HR 3.18, 95% CI 1.06–9.56], but not for stroke or systemic embolism [HR 0.94, 95% CI 0.40–2.24], or bleeding requiring hospitalization [HR 2.00, 95% CI 0.93–4.28]. 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 15–29 group, in Japanese non-valvular AF patients aged ≥75 years. Cumulative incidence rates of events Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Bristol-Myers Squibb