Bradley Marie, Welch Emily C, Eworuke Efe, Graham David J, Zhang Rongmei, Huang Ting-Ying
Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
J Gen Intern Med. 2020 Dec;35(12):3597-3604. doi: 10.1007/s11606-020-06180-8. Epub 2020 Sep 28.
A previous FDA study reported a favorable benefit risk for apixaban compared with warfarin for stroke prevention in older non-valvular atrial fibrillation (NVAF) patients (≥ 65 years). However, it remains unclear whether this favorable benefit risk persists in other populations including younger users. We examined if a similar benefit risk was observed in the Sentinel System and if it varied by age group.
To examine the risk of ischemic stroke, gastrointestinal (GI) bleeding, and intracranial hemorrhage (ICH) in apixaban users compared with warfarin users in Sentinel Distributed Database (SDD).
A retrospective new user cohort study was conducted among patients, 21 years and older initiating apixaban and warfarin for NVAF, between December 28, 2012, and June 30, 2018, in the SDD.
Cox proportional hazard regression was used to estimate the hazard ratios (HR) and 95% confidence intervals (95% CI) for each outcome (ischemic stroke, GI bleeding, and ICH) in propensity score matched apixaban users compared with the warfarin users. Subgroup analyses by age (21-64, 65-74, and 75+ years) were conducted.
After matching, 55.3% and 58.4% (n = 55,038) of the apixaban and warfarin users were included in the main analysis. GI bleeding was the most common outcome. The HR (95% CI) for GI bleeding, ICH, and ischemic stroke in apixaban users compared with warfarin users were 0.57 (0.50-0.66), 0.53 (0.40-0.70), and 0.56 (0.45-0.71) respectively. The reduced risk of these outcomes in apixaban compared with warfarin users persisted across age groups.
In NVAF patients of all ages initiating either apixaban or warfarin for stroke prevention in the Sentinel System, apixaban was associated with a decreased risk of GI bleeding, ICH, and ischemic stroke compared with warfarin. Among patients less than 65 years of age, apixaban use was associated with a decreased risk of GI bleeding and ischemic stroke.
美国食品药品监督管理局（FDA）此前的一项研究报告称，在老年非瓣膜性心房颤动（NVAF）患者（≥65岁）中，与华法林相比，阿哌沙班在预防中风方面具有良好的效益风险比。然而，在包括年轻使用者在内的其他人群中，这种良好的效益风险比是否持续存在仍不清楚。我们研究了在哨兵系统中是否观察到类似的效益风险比，以及它是否因年龄组而异。
在哨兵分布式数据库（SDD）中，比较阿哌沙班使用者与华法林使用者发生缺血性中风、胃肠道（GI）出血和颅内出血（ICH）的风险。
在2012年12月28日至2018年6月30日期间，对SDD中21岁及以上因NVAF开始使用阿哌沙班和华法林的患者进行了一项回顾性新使用者队列研究。
采用Cox比例风险回归分析，估计倾向评分匹配的阿哌沙班使用者与华法林使用者相比，每种结局（缺血性中风、GI出血和ICH）的风险比（HR）和95%置信区间（95%CI）。按年龄（21 - 64岁、65 - 74岁和75岁及以上）进行亚组分析。
匹配后，主要分析纳入了55.3%的阿哌沙班使用者和58.4%（n = 55,038）的华法林使用者。GI出血是最常见的结局。与华法林使用者相比，阿哌沙班使用者发生GI出血、ICH和缺血性中风的HR（95%CI）分别为0.57（0.50 - 0.66）、0.53（0.40 - 0.70）和0.56（0.45 - 0.71）。与华法林使用者相比，阿哌沙班降低这些结局风险的效果在各年龄组中均持续存在。
在哨兵系统中，所有年龄因中风预防而开始使用阿哌沙班或华法林的NVAF患者中，与华法林相比，阿哌沙班与GI出血、ICH和缺血性中风风险降低相关。在年龄小于65岁的患者中，使用阿哌沙班与GI出血和缺血性中风风险降低相关。
