School of Life Course and Population Sciences, King's College London, London, UK.
Neuroepidemiology. 2024;58(1):1-14. doi: 10.1159/000534596. Epub 2023 Oct 17.
Current evidence regarding the clinical outcomes of non-vitamin K oral anticoagulants (NOACs) versus warfarin in patients with atrial fibrillation (AF) and previous stroke is inconclusive, especially in patients with previous intracranial haemorrhage (ICrH). We aim to undertake a systematic review and meta-analysis assessing the effectiveness and safety of NOACs versus warfarin in AF patients with a history of stroke.
We searched studies published up to December 10, 2022, on PubMed, Medline, Embase, and Cochrane Central Register of Controlled Trials. Studies on adults with AF and previous ischaemic stroke (IS) or IrCH receiving either NOACs or warfarin and capturing outcome events (thromboembolic events, ICrH, and all-cause mortality) were eligible for inclusion.
Six randomized controlled trials (RCTs) (including 19,489 patients with previous IS) and fifteen observational studies (including 132,575 patients with previous IS and 13,068 patients with previous ICrH) were included. RCT data showed that compared with warfarin, NOACs were associated with a significant reduction in thromboembolic events (odds ratio [OR]: 0.85, 95% confidence interval [CI]: 0.75-0.96), ICrH (OR: 0.57, 95% CI: 0.36-0.90), and all-cause mortality (OR: 0.88, 95% CI: 0.80-0.98). In analysing observational studies, similar results were retrieved. Moreover, patients with previous ICrH had a lower OR on thromboembolic events than those with IS (OR: 0.66, 95% CI: 0.46-0.95 vs. OR: 0.80, 95% CI: 0.70-0.93) in the comparison between NOACs and warfarin.
Observational data showed that in AF patients with previous stroke, NOACs showed better clinical performance compared to warfarin and the benefits of NOACs were more pronounced in patients with previous IrCH versus those with IS. RCT data also showed NOACs are superior to warfarin. However, current RCTs only included AF patients who survived an IS, and further large RCTs focused on patients with previous ICrH are warranted.
目前关于非维生素 K 口服抗凝剂 (NOACs) 与华法林在伴有心房颤动 (AF) 和既往卒中患者中的临床结局的证据尚无定论，尤其是在既往有颅内出血 (ICH) 的患者中。我们旨在进行一项系统评价和荟萃分析，评估 AF 患者既往有卒中史时使用 NOACs 与华法林的疗效和安全性。
我们在 PubMed、Medline、Embase 和 Cochrane 对照试验中心注册库中检索了截至 2022 年 12 月 10 日发表的研究。纳入的研究对象为接受 NOACs 或华法林治疗且有既往缺血性卒中 (IS) 或 ICrH 的 AF 成年患者，同时纳入了结局事件（血栓栓塞事件、ICH 和全因死亡率）。
纳入了 6 项随机对照试验（RCTs）（包括 19489 例既往有 IS 的患者）和 15 项观察性研究（包括 132575 例既往有 IS 的患者和 13068 例既往有 ICrH 的患者）。RCT 数据显示，与华法林相比，NOACs 显著降低了血栓栓塞事件（比值比 [OR]：0.85，95%置信区间 [CI]：0.75-0.96）、ICH（OR：0.57，95% CI：0.36-0.90）和全因死亡率（OR：0.88，95% CI：0.80-0.98）。在分析观察性研究时，也得到了类似的结果。此外，与 IS 相比，既往有 ICrH 的患者在 NOACs 与华法林比较时，血栓栓塞事件的 OR 更低（OR：0.66，95% CI：0.46-0.95 vs. OR：0.80，95% CI：0.70-0.93）。
观察性数据表明，在既往有卒中的 AF 患者中，NOACs 较华法林具有更好的临床疗效，且在既往有 ICrH 的患者中，NOACs 的获益较 IS 患者更为显著。RCT 数据也表明，NOACs 优于华法林。然而，目前的 RCT 仅纳入了存活 IS 的 AF 患者，需要进一步开展针对既往有 ICrH 患者的大型 RCT。
