凝血因子Ⅺa（FXIa）抑制剂与卒中二级预防。
完整摘要 · 中文译文
综述目的：非心源性栓塞性缺血性卒中患者尽管接受抗血小板治疗，仍面临显著的复发残余风险，而传统抗凝治疗因不可接受的出血风险过高而不适用。激活的凝血因子XI（FXIa）抑制有望在保留止血功能的同时实现抗凝疗效。我们结合关键的OCEANIC-STROKE试验，评估FXIa抑制剂在卒中二级预防中的证据。 近期发现：asundexian和milvexian的II期试验在安全性方面令人放心，但在影像学终点方面为中性结果，表明隐匿性梗死并非良好的替代终点。在III期OCEANIC-STROKE试验中，asundexian联合单药或双联抗血小板治疗可使复发性缺血性卒中降低26%，且在各亚型间结果一致，未增加大出血或颅内出血。相比之下，asundexian在心房颤动中劣于阿哌沙班，这一结果可归因于剂量、对照药物和研究背景的差异。与此一致，单克隆抗体abelacimab可实现近乎完全的FXIa抑制，在心房颤动中与利伐沙班相比减少了出血，但其对血栓栓塞事件的影响尚未确立。 总结：FXIa抑制是首个在不增加出血代价的情况下预防非心源性栓塞性缺血性卒中后卒中复发的抗凝策略。尚待进一步试验证实该类药物的类效应，并需解答治疗时长、更深程度抑制及其他心血管适应症中的应用等问题。
完整摘要 · 英文原文
PURPOSE OF REVIEW: Patients with noncardioembolic ischemic stroke face a substantial residual risk of recurrence despite antiplatelet therapy, while conventional anticoagulation is unsuitable due to an unacceptably high bleeding risk. Activated factor XI (FXIa) inhibition promises anticoagulant efficacy while sparing hemostasis. We appraise the evidence of FXIa-inhibitors in secondary stroke prevention considering the pivotal OCEANIC-STROKE trial. RECENT FINDINGS: Phase-2 trials of asundexian and milvexian were reassuring on safety but neutral on imaging-based endpoints, establishing that covert infarcts are a poor surrogate. In the phase-3 OCEANIC-STROKE trial, asundexian added to single or dual antiplatelet therapy reduced recurrent ischemic stroke by 26%, consistently across subtypes, without any excess of major bleeding or intracranial hemorrhage. By contrast, asundexian was inferior to apixaban in atrial fibrillation, a result attributable to dose, comparator, and setting. Consistent with this, the monoclonal antibody abelacimab, which achieves near-complete FXIa-inhibition, reduced bleeding relative to rivaroxaban in atrial fibrillation, though its effect on thromboembolic events has not been established. SUMMARY: FXIa-inhibition is the first anticoagulant strategy preventing recurrent stroke after noncardioembolic ischemic stroke without a bleeding penalty. Confirmation of a class effect from further trials is awaited, alongside questions of duration, deeper inhibition, and use in other cardiovascular indications.