口服 XIa 因子抑制剂用于非心源性栓塞性缺血性卒中或高危短暂性脑缺血发作后的二级预防：系统评价与荟萃分析。
完整摘要 · 中文译文
引言：对于近期发生非心源性栓塞性缺血性卒中或高危短暂性脑缺血发作（TIA）的患者，尽管接受抗血小板治疗，仍存在复发事件的风险。口服因子XIa（FXIa）抑制剂可能降低血栓形成风险同时限制出血，但其辅助治疗的疗效和安全性仍需明确。 方法：检索PubMed、Embase、Cochrane Library/CENTRAL及ClinicalTrials.gov数据库，时间截至2026年5月，纳入在抗血小板治疗基础上加用口服因子XIa抑制剂的随机、双盲、安慰剂对照试验。主要疗效结局为复发性缺血性卒中，主要安全性结局为大出血。采用随机效应模型合并风险比（RR）及其95%置信区间（CI）。 结果：三项试验共随机分配16,501名受试者，其中14,239名纳入主要选定剂量疗效分析。因子XIa抑制降低了复发性缺血性卒中风险（413/6927 对 579/7312；RR 0.74，95% CI 0.65-0.84；I² = 0%；p < 0.00001）。在大出血（RR 1.12，95% CI 0.87-1.44）、大出血或临床相关非大出血（RR 1.40，95% CI 0.91-2.15）、临床相关非大出血（RR 1.49，95% CI 0.85-2.60）、轻微或不可干预出血（RR 0.94，95% CI 0.84-1.05）、颅内或脑内出血（RR 1.16，95% CI 0.75-1.79）或致死性出血（RR 1.75，95% CI 0.74-4.17）方面未观察到统计学显著差异；然而，多项出血结局的置信区间较宽，未排除临床重要危害的可能性。在全剂量敏感性分析中结果保持一致（RR 0.77，95% CI 0.68-0.86；I2 = 0%）。 结论：在近期非心源性栓塞性缺血性卒中或高危短暂性脑缺血发作且接受抗血小板治疗的患者中，汇总的随机证据显示，口服XIa因子抑制剂可减少复发性缺血性卒中的发生；然而，该估计值主要由3期asundexian试验驱动，限制了对于不同XIa因子抑制剂间普遍适用性的确定性。大出血及其他安全性结局未显著增加，但罕见事件的估计值不精确，临床上重要的危害不能排除。
完整摘要 · 英文原文
INTRODUCTION: Patients with recent noncardioembolic ischemic stroke or high-risk transient ischemic attack (TIA) remain at risk of recurrent events despite antiplatelet therapy. Oral factor XIa (FXIa) inhibitors may reduce thrombotic risk while limiting bleeding, but their adjunctive efficacy and safety require clarification. METHODS: PubMed, Embase, Cochrane Library/CENTRAL, and ClinicalTrials.gov were searched through May 2026 for randomized, double-blind, placebo-controlled trials of oral FXIa inhibitors added to antiplatelet therapy. Primary efficacy and safety outcomes were recurrent ischemic stroke and major bleeding. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models. RESULTS: Three trials randomized 16,501 participants overall, of whom 14,239 contributed to the primary selected-dose efficacy analysis. FXIa inhibition reduced recurrent ischemic stroke (413/6927 vs. 579/7312; RR 0.74, 95% CI 0.65-0.84; I2 = 0%; p < 0.00001). No statistically significant differences were observed in major bleeding (RR 1.12, 95% CI 0.87-1.44), major or clinically relevant non-major bleeding (RR 1.40, 95% CI 0.91-2.15), clinically relevant non-major bleeding (RR 1.49, 95% CI 0.85-2.60), minor or non-actionable bleeding (RR 0.94, 95% CI 0.84-1.05), intracranial or intracerebral hemorrhage (RR 1.16, 95% CI 0.75-1.79), or fatal bleeding (RR 1.75, 95% CI 0.74-4.17); however, confidence intervals for several bleeding outcomes were wide and did not exclude clinically important harm. Findings remained consistent in the all-dose sensitivity analysis (RR 0.77, 95% CI 0.68-0.86; I2 = 0%). CONCLUSIONS: In patients with recent noncardioembolic ischemic stroke or high-risk TIA receiving antiplatelet therapy, pooled randomized evidence showed a reduction in recurrent ischemic stroke with oral FXIa inhibition; however, the estimate was predominantly driven by the phase 3 asundexian trial, limiting certainty regarding generalization across individual FXIa inhibitors. Major bleeding and other safety outcomes were not significantly increased, although rare-event estimates were imprecise and clinically important harm cannot be excluded.