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

<b>Objective:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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; <i>p</i> p = .001) and stroke/SE (HR 0.637, 95% CI 0.478–0.850; <i>p</i> = .002). <b>Conclusions:</b> 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.

<b>研究目的：</b> 本研究旨在探讨日本非瓣膜性心房颤动（nonvalvular atrial fibrillation, NVAF）患者的出血事件与卒中/体循环栓塞（systemic embolism, SE）发生风险，重点关注阿哌沙班（apixaban）的初始给药剂量及患者年龄。<b>研究方法：</b> 本回顾性队列研究采用日本314家急性医疗医院的去标识化电子健康记录理赔数据。研究纳入在180天洗脱期内无抗凝药物用药史的、新启动华法林（warfarin）或阿哌沙班治疗的NVAF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（propensity-score matching）平衡阿哌沙班组与华法林组的患者基线特征。<b>研究结果：</b> 本研究共纳入31006例符合条件的患者，经匹配后得到阿哌沙班组与华法林组共11972对匹配队列。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%的患者接受减量剂量（2.5mg每日两次）治疗。华法林组与阿哌沙班组的主要出血、任一出血及卒中/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，阿哌沙班组的任一出血风险（风险比（hazard ratio, HR）0.809，95%置信区间（confidence interval, CI）0.731–0.895；*p*=0.001）与卒中/SE风险（HR 0.637，95%CI 0.478–0.850；*p*=0.002）均显著降低。<b>研究结论：</b> 本项来自临床实践的观察性数据，大体验证了阿哌沙班用于NVAF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。