- 期刊
第XI因子抑制劑：新抗凝劑在急性缺血性腦中風的效益
Factor XI inhibitors: The New Anticoagulant for Acute Ischemic Stroke
並列摘要
Coagulation factor XI (FXI) of the intrinsic pathway plays an important role in the process of pathological thrombosis but has relatively limited effect on physiological haemostasis. Hence, it has been suggested that inhibition of activated FXI (FXIa) can prevent thromembolic disorders and minimize the risk of bleeding. The new FXIa inhibitor, asundexian, has been recently published in the phase II randomized placebo-controlled trial PACIFIC-Stroke, which added a once-daily oral anticoagulant asundexian to standard antiplatelet therapy (single- or dual-antiplatelet) in acute non-cardiogenic ischemic stroke patients for secondary stroke prevention. There were no differences between asundexian (10 mg, 20 mg, and 50 mg daily) and placebo in primary efficacy composite outcomes, including recurrent ischemic stroke, transient ischemic attack, and covert cerebral infarction. But there was also no group difference on the primary safety endpoint of major and clinically relevant non-major bleeding. A notable sub-analysis found that, especially in those with large artery atherosclerosis, FXIa inhibition with asundexian reduced recurrent ischemic stroke and transient ischemic attack compared with placebo without increased bleeding. This result needs to be validated in a phase III randomized controlled trial to be applied to secondary prevention of ischemic stroke. Other FXIa inhibitor drugs, including SHR22857, ONO-76848, BMS 986177 (Milvexian), have all published the phase I trials in healthy people, with good tolerance, no major adverse reactions, and comparable bleeding time as the placebo group. Ongoing clinical trials of FXIa inhibitors are also being studied in patients with atrial fibrillation, acute myocardial infarction, and severe renal failure. FXIa inhibitors are a new class of oral anticoagulant drugs that have shown the potential and safety as an add-on therapy for high-risk thromboembolic patients.