观点：我们从因子XI/因子XIa抑制剂试验中学到了什么。
完整摘要 · 中文译文
在过去十年中，多种靶向因子XI（FXI）/XIa的药物管道已进入临床开发阶段，包括口服小分子抑制剂、单克隆抗体、反义寡核苷酸和小干扰RNA。在早期和晚期临床试验中，这些药物总体上显示出良好的安全性特征，大出血发生率持续较低，即使与抗血小板治疗联用或与标准抗凝药相比也是如此。然而，疗效信号因临床场景而异。在骨科手术后静脉血栓栓塞预防和缺血性卒中二级预防中，FXI/XIa抑制显示出令人鼓舞的抗血栓活性。相比之下，在心房颤动、急性冠脉综合征和癌症相关血栓形成中的试验结果疗效不一，凸显了内源性通路抑制在高凝血酶生成或血小板驱动性血栓形成条件下可能存在的局限性。总体而言，这些发现将FXI/XIa抑制剂定位为针对特定适应症的抗血栓治疗中可能出现的范式转变，正在进行的3期研究有望进一步明确其在不同血栓性疾病中的临床角色和最优使用方式。
完整摘要 · 英文原文
Over the past decade, a diverse pipeline of factor XI (FXI)/XIa-targeting agents has entered clinical development, including oral small-molecule inhibitors, monoclonal antibodies, antisense oligonucleotides, and small interfering RNAs. Across early- and late-phase clinical trials, these agents have generally shown a favorable safety profile, with consistently low rates of major bleeding, even when used with antiplatelet therapy or compared with standard anticoagulants. However, efficacy signals have varied by clinical setting. In venous thromboembolism prophylaxis after orthopedic surgery and in secondary stroke prevention, FXI/XIa inhibition has shown encouraging antithrombotic activity. In contrast, trials in atrial fibrillation, acute coronary syndrome, and cancer-associated thrombosis have yielded mixed efficacy results, highlighting potential limitations of intrinsic pathway inhibition in conditions with high thrombin generation or platelet-driven thrombosis. Collectively, these findings position FXI/XIa inhibitors as a potential paradigm shift in antithrombotic therapy for targeted indications, with ongoing phase 3 studies expected to further define their clinical role and optimal use across diverse thrombotic disorders.