Safety and effectiveness of apixaban in comparison to warfarin in patients with nonvalvular atrial fibrillation: a propensity-matched analysis from Japanese administrative claims data

Objective: To investigate the risk of bleeding events and stroke/systemic embolism (SE) among Japanese patients with nonvalvular atrial fibrillation (NVAF), focusing on the initial dosage of apixaban and patient age.
Methods: This retrospective cohort study used de-identified electronic health records based claims data from 314 acute-care hospitals in Japan. NVAF patients newly initiated on warfarin or apixaban, with no prescription during the 180-day blanking period, were eligible. Patients were allocated to receive warfarin or 5 or 2.5 mg twice daily (BID) apixaban. One-to-one propensity-score matching was used to balance patient characteristics between apixaban and warfarin.
Results: Among 31,006 eligible patients, 11,972 matched pairs were identified for apixaban versus warfarin. Mean age ± standard deviation was 77.7 ± 10.0 and 77.6 ± 10.0 years and CHADS2 score was 2.2 ± 1.4 and 2.2 ± 1.4 for warfarin and apixaban, respectively. In the apixaban cohort, 39.4% of patients received the standard dose (5 mg BID) and 60.6% received the reduced dose (2.5 mg BID). Incidence rates (events per 100 person-years) of major bleeding, any bleeding and stroke/SE were 3.7, 23.1 and 3.1, and 2.5, 18.6 and 2.0 for warfarin and apixaban cohorts, respectively. Apixaban was associated with a significantly lower risk of any bleeding (hazard ratio [HR] 0.809, 95% confidence interval [CI] 0.731–0.895; p < .001), major bleeding (HR 0.655, 95% CI 0.505–0.849; p = .001) and stroke/SE (HR 0.637, 95% CI 0.478–0.850; p = .002).
Conclusions: Our observational data from clinical practice broadly confirms the safety and efficacy results of pivotal randomized controlled trials of apixaban for stroke prevention among NVAF patients.

研究目的：本研究旨在探究日本非瓣膜性心房颤动（nonvalvular atrial fibrillation, NVAF）患者的出血事件及卒中/体循环栓塞（stroke/systemic embolism, SE）发生风险，重点关注阿哌沙班（apixaban）的初始给药剂量与患者年龄。

研究方法：本回顾性队列研究采用日本314所急性护理医院的去标识化电子健康记录理赔数据。纳入标准为：首次启动华法林（warfarin）或阿哌沙班（apixaban）治疗、且在180天洗脱期内无相关处方记录的非瓣膜性心房颤动患者。将患者分为华法林组、阿哌沙班5mg每日两次（twice daily, BID）组与阿哌沙班2.5mg每日两次组。采用1:1倾向得分匹配法平衡阿哌沙班组与华法林组的患者基线特征。

研究结果：共计纳入31006例符合标准的患者，其中阿哌沙班组与华法林组共匹配得到11972对患者。华法林组与阿哌沙班组的平均年龄±标准差分别为77.7±10.0岁与77.6±10.0岁，CHADS2评分分别为2.2±1.4与2.2±1.4。阿哌沙班组中，39.4%的患者接受标准剂量（5mg每日两次）治疗，60.6%接受减量剂量（2.5mg每日两次）治疗。华法林组与阿哌沙班组的大出血、任何出血事件及卒中/SE的发生率（每100人年事件数）分别为3.7、23.1、3.1与2.5、18.6、2.0。与华法林组相比，阿哌沙班组的任何出血事件（风险比[hazard ratio, HR] 0.809，95%置信区间[confidence interval, CI] 0.731–0.895；p<0.001）、大出血（HR 0.655，95%CI 0.505–0.849；p=0.001）及卒中/SE（HR 0.637，95%CI 0.478–0.850；p=0.002）风险均显著降低。

研究结论：本项来自临床实践的观察性数据，基本验证了阿哌沙班用于非瓣膜性心房颤动患者卒中预防的关键随机对照试验所得出的安全性与有效性结果。