背景:关于非维生素K口服抗凝药(NOAC)与华法林在房颤(AF)和既往卒中患者中的临床结局的现有证据尚无定论,尤其是既往有颅内出血(ICrH)的患者。我们旨在进行系统评价和荟萃分析,评估NOACs与华法林在有卒中病史的房颤患者中的有效性和安全性。
方法:我们搜索了截至2022年12月10日在PubMed上发表的研究,Medline,Embase和Cochrane中央控制试验登记册。对患有房颤和既往缺血性卒中(IS)或IrCH的成年人接受NOAC或华法林并捕获结果事件(血栓栓塞事件,ICrH,和全因死亡率)符合纳入条件。
结果:纳入了6项随机对照试验(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,NOAC与血栓栓塞事件的显著减少相关(OR0.85,95%CI0.75-0.96),ICrH(OR0.57,95%CI0.36-0.90)和全因死亡率(OR0.88,95%CI0.80至0.98)。在分析观察性研究时,检索到类似的结果。此外,在NOAC和华法林之间的比较中,既往有ICrH的患者在血栓栓塞事件上的OR值低于有IS的患者(OR0.66,95%CI0.46-0.95vs.OR0.80,95%CI0.70-0.93).
结论:观察数据显示,在既往卒中的房颤患者中,与华法林相比,NOACs显示出更好的临床表现,并且在先前的IrCH患者中与IS患者相比,NOACs的益处更为明显。RCT数据还显示NOACs优于华法林。然而,目前的RCTs仅包括在IS中存活的AF患者,并且有必要进一步将大型RCTs重点放在先前患有ICrH的患者上.
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.