Emara Ahmed, Gadelmawla Ahmed Farid, Emara Mohamed, Murad Mohamed R, Elgendy Mohamed S, Ellebedy Mohamed, Hemmeda Lina, Aldemerdash Mohamed A, Mohammed Ahmed Abduljalil, Abdelazeem Basel
Faculty of Medicine, Al Azhar University, Cairo, Egypt.
Medical Research Group of Egypt, Negida Academy LLC, Arlington, MA, USA.
Naunyn Schmiedebergs Arch Pharmacol. 2025 May 16. doi: 10.1007/s00210-025-04259-9.
Direct oral anticoagulants (DOACs) prevent stroke in atrial fibrillation (AF) but are associated with an increased risk of major bleeding. Factors XI/XIa (FXI) inhibitors, such as Abelacimab and Asundexian, offer a promising alternative. This meta-analysis compares FXI/XIa inhibitors' safety and efficacy versus DOACs in AF with stroke risk. A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed from PubMed, Scopus, Cochrane, and Web of Science up to March 2025. The analysis presented risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI) using RevMan v5.4. Three RCTs involving 16,852 patients were included, with 8777 (52.1%) receiving FXI inhibitors which significantly reduced the risk of major bleeding (0.4% vs. 1.0%, RR 0.31, 95% CI 0.21-0.46, p < 0.00001) and minor bleeding (3.3% vs. 4.7%, RR 0.66, 95% CI 0.47-0.93; p = 0.02) compared with DOACs. However, FXI inhibitors were associated with a significantly higher risk of stroke or systemic embolism (1.4% vs. 0.4%, RR 3.17, 95% CI 2.18-4.62, p < 0.00001). Safety outcomes showed no difference in total adverse events (AEs) (p = 0.91), serious AEs (p = 0.4768), and all-cause mortality (p = 0.15). In conclusion, current evidence suggests that FXI inhibitors significantly reduce major and minor bleeding events in AF patients at risk of thromboembolic disorders compared to DOACs. However, they are associated with a significant increase in stroke or systemic embolism risk. Further large-scale RCTs are needed to confirm these findings.
直接口服抗凝剂（DOACs）可预防心房颤动（AF）患者发生中风，但会增加大出血风险。凝血因子XI/XIa（FXI）抑制剂，如阿贝西单抗和阿孙德昔单抗，提供了一种有前景的替代方案。这项荟萃分析比较了FXI/XIa抑制剂与DOACs在有中风风险的AF患者中的安全性和有效性。截至2025年3月，从PubMed、Scopus、Cochrane和科学网对随机对照试验（RCTs）进行了系统评价和荟萃分析。该分析使用RevMan v5.4给出了二分类结局的风险比（RR）及95%置信区间（CI）。纳入了三项涉及16852例患者的RCT，其中8777例（52.1%）接受FXI抑制剂治疗，与DOACs相比，其显著降低了大出血风险（0.4%对1.0%，RR 0.31，95%CI 0.21 - 0.46，p < 0.00001）和小出血风险（3.3%对4.7%，RR 0.66，95%CI 0.47 - 0.93；p = 0.02）。然而，FXI抑制剂与中风或全身性栓塞风险显著升高相关（1.4%对0.4%，RR 3.17，95%CI 2.18 - 4.62，p < 0.00001）。安全性结局显示，在总不良事件（AE）（p = 0.91）、严重AE（p = 0.4768）和全因死亡率（p = 0.15）方面无差异。总之，目前的证据表明，与DOACs相比，FXI抑制剂可显著降低有血栓栓塞性疾病风险的AF患者的大出血和小出血事件。然而，它们与中风或全身性栓塞风险的显著增加相关。需要进一步的大规模RCT来证实这些发现。
