Wang Zixuan, Matthewman Julian, Tazare John, Yu Qiuyan, Cheung Ka Shing, Chui Celine S L, Chan Esther W Y, Bhaskaran Krishnan, Smeeth Liam, Wong Ian C K, Douglas Ian J, Wong Angel Y S
Department of Non-Communicable Disease Epidemiology, Faculty of Epidemiology & Population Health, London, School of Hygiene and Tropical Medicine , London, UK.
Laboratory of Data Discovery for Health (D24H), Hong Kong, China.
BMC Med. 2024 Dec 23;22(1):597. doi: 10.1186/s12916-024-03808-y.
Direct oral anticoagulants (DOACs) have been reported to be associated with a higher risk of mortality compared with an older alternative, warfarin using primary care data in the United Kingdom (UK). However, other studies observed contradictory findings. We therefore aimed to investigate the association between mortality and warfarin, compared with DOACs.
We conducted cohort studies using UK Clinical Practice Research Datalink (CPRD) Aurum and Hong Kong Clinical Data Analysis and Reporting System (CDARS) to identify the association between warfarin and hazard of mortality, compared to DOACs. Individuals with non-valvular atrial fibrillation aged ≥ 18 years who had first anticoagulant therapy (warfarin or DOAC) during 1/1/2011-31/12/2019 were included.
Compared with DOAC use, a lower hazard of all-cause mortality was found in warfarin users (hazard ratio (HR) = 0.81, 95% confidence interval (CI) = 0.77-0.86) in CPRD; while a higher hazard was observed in warfarin users (HR = 1.31, 95% CI = 1.24-1.39) in CDARS, versus DOAC users. In our exploratory analysis, consistent results were seen in both databases when stratified warfarin users by time in therapeutic range (TTR) using post-baseline measurements: a lower hazard of all-cause mortality in warfarin users with TTR ≥ 65% (CPRD: HR = 0.68, 95% CI = 0.65-0.72; CDARS: HR = 0.86, 95% CI = 0.77-0.96) and increased hazard in warfarin users with TTR < 65% (CPRD: HR = 1.14, 95% CI = 1.05-1.23; CDARS: HR = 1.59, 95% CI = 1.50-1.69), versus DOAC users.
The differences in hazard of all-cause mortality associated with warfarin compared with DOAC, in part may depend on anticoagulation control in warfarin users. Notably, this study is unable to establish a causal relationship between warfarin and mortality stratified by TTR, versus DOACs, requiring future studies for further investigation.
据报道，与一种较老的替代药物华法林相比，使用英国初级保健数据显示，直接口服抗凝剂（DOACs）的死亡风险更高。然而，其他研究观察到了相互矛盾的结果。因此，我们旨在研究华法林与DOACs相比在死亡率方面的关联。
我们使用英国临床实践研究数据链（CPRD）Aurum和香港临床数据分析与报告系统（CDARS）进行队列研究，以确定华法林与DOACs相比在死亡率方面的关联。纳入2011年1月1日至2019年12月31日期间首次接受抗凝治疗（华法林或DOAC）的年龄≥18岁的非瓣膜性心房颤动患者。
与使用DOAC相比，CPRD中使用华法林的患者全因死亡率风险较低（风险比（HR）=0.81，95%置信区间（CI）=0.77-0.86）；而在CDARS中，与使用DOAC的患者相比，使用华法林的患者风险较高（HR=1.31，95%CI=1.24-1.39）。在我们的探索性分析中，当使用基线后测量值按治疗范围内时间（TTR）对华法林使用者进行分层时，两个数据库中均观察到了一致的结果：TTR≥65%的华法林使用者全因死亡率风险较低（CPRD：HR=0.68，95%CI=0.65-0.72；CDARS：HR=0.86，95%CI=0.77-0.96），而TTR<65%的华法林使用者风险增加（CPRD：HR=1.14，95%CI=1.05-1.23；CDARS：HR=1.59，95%CI=1.50-1.69），与使用DOAC的患者相比。
与DOAC相比，华法林相关的全因死亡率风险差异，部分可能取决于华法林使用者的抗凝控制情况。值得注意的是，本研究无法确定按TTR分层的华法林与DOACs在死亡率之间的因果关系，需要未来的研究进一步调查。
