Shahid Sufyan, Iqbal Minahil, Shahabi Mariam, Ali Muhammad Abdullah, Khan Allahdad, Shahid Muhammad Ali, Iqbal Hamyial, Shahid Khadija, Khalid Salman
Khawaja Muhammad Safdar Medical College, Sialkot, Pakistan.
Allama Iqbal Medical College, Lahore, Pakistan.
Cardiovasc Drugs Ther. 2025 Jun 25. doi: 10.1007/s10557-025-07741-x.
Direct oral anticoagulants (DOACs) are the standard treatment for reducing thromboembolic risk in patients with atrial fibrillation (AF); however, bleeding remains a major concern. Factor XIa inhibitors have emerged as a potential alternative, but evidence about their therapeutic potential remains unclear. We performed a systematic review and meta-analysis to evaluate the comparative efficacy and safety of Factor XIa inhibitors versus DOACs for AF.
PubMed, Embase, and Cochrane Library were systematically searched until February 15, 2025, to identify RCTs comparing Factor XIa inhibitors with DOACs in AF patients. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a random-effects model. Statistical analysis was performed in RevMan 5.4 with p-value < 0.05 considered significant, and meta-analyses were conducted using a bivariate random-effects model. Study heterogeneity was measured using I statistics, and study quality was assessed using the revised Cochrane risk-of-bias (RoB 2) tool.
Three RCTs comprising 16,845 patients (41% females) were included. The mean age of the participants was 74 years. Factor XIa inhibitors were associated with a significantly higher risk of ischemic stroke (RR: 3.32; 95% CI: 2.24-4.90, I: 0%, p < 0.00001) but a lower risk of major or clinically relevant non-major (CRNM) bleeding (RR: 0.41; 95% CI: 0.33-0.49, I: 0%, p < 0.00001) and minor bleeding (RR: 0.68; 95% CI: 0.49-0.93, I: 64%, p = 0.02) compared to DOACs. However, there was no significant difference in the risk of all-cause mortality, cardiovascular mortality, or hemorrhagic stroke between the two groups.
Factor XIa inhibitors are associated with a reduced risk of major, minor, and clinically relevant non-major bleeding than DOACs but simultaneously increase the risk of ischemic stroke. No significant differences were found in the risk of hemorrhagic stroke or overall mortality rates compared to DOACs.
直接口服抗凝剂（DOACs）是降低心房颤动（AF）患者血栓栓塞风险的标准治疗方法；然而，出血仍然是一个主要问题。因子XIa抑制剂已成为一种潜在的替代药物，但其治疗潜力的证据仍不明确。我们进行了一项系统评价和荟萃分析，以评估因子XIa抑制剂与DOACs治疗AF的疗效和安全性。
系统检索PubMed、Embase和Cochrane图书馆，直至2025年2月15日，以确定比较因子XIa抑制剂与DOACs治疗AF患者的随机对照试验（RCT）。使用随机效应模型汇总95%置信区间（CI）的风险比（RR）。在RevMan 5.4中进行统计分析，p值<0.05被认为具有统计学意义，并使用双变量随机效应模型进行荟萃分析。使用I统计量测量研究异质性，并使用修订的Cochrane偏倚风险（RoB 2）工具评估研究质量。
纳入了三项RCT，共16845例患者（41%为女性）。参与者的平均年龄为74岁。与DOACs相比，因子XIa抑制剂与缺血性中风风险显著升高相关（RR：3.32；95%CI：2.24-4.90，I：0%，p<0.00001），但主要或临床相关非主要（CRNM）出血风险较低（RR：0.41；95%CI：0.33-0.49，I：0%p<0.00001）和轻微出血风险较低（RR：0.68；95%CI：0.49-0.93，I：64%，p=0.02）。然而两组在全因死亡率、心血管死亡率或出血性中风风险方面无显著差异。
与DOACs相比，因子XIa抑制剂与主要、轻微和临床相关非主要出血风险降低相关，但同时增加了缺血性中风风险。与DOACs相比，出血性中风风险或总死亡率无显著差异。
