急性冠脉综合征事件后使用Milvexian联合抗血小板治疗
完整摘要 · 中文译文
背景：急性冠脉综合征事件后，患者复发性缺血事件的风险增加。Milvexian 是一种口服 XIa 因子抑制剂，可在出血风险极低的情况下降低主要不良临床事件的风险。 方法：在这项 3 期、随机、安慰剂对照试验中，我们评估了在急性冠脉综合征事件后 7 天内，在标准抗血小板治疗基础上加用 milvexian 的疗效和安全性。患者以 1:1 的比例被分配接受口服 milvexian（25 mg，每日两次）或匹配的安慰剂。主要疗效结局是心血管死亡、心肌梗死或缺血性卒中的复合结局，采用至事件发生时间分析进行评估。主要安全性结局是出血学术研究联合会（BARC）3c 型或 5 型出血（颅内出血或影响视力的眼内出血或致死性出血）。 结果：在基于 556 例已裁定疗效终点进行的计划内中期分析后，该试验因无效而终止。共入组 14,194 例患者，其中 7094 例被分配接受 milvexian，7100 例被分配接受安慰剂。中位随访 12.2 个月后，milvexian 组 384 例患者（5.4%）和安慰剂组 365 例患者（5.1%）发生了主要疗效结局事件（风险比，1.05；95% 置信区间，0.91 至 1.21；P = 0.50）。milvexian 组 23 例患者（0.3%）和安慰剂组 22 例患者（0.3%）发生了 BARC 3c 型或 5 型出血（P = 0.88）。 结论：在近期发生急性冠状动脉综合征事件的患者中，与安慰剂相比，milvexian并未降低心血管死亡、心肌梗死或缺血性卒中的风险，但也没有增加颅内出血或致死性出血的风险。（由Janssen Research and Development和Bristol Myers Squibb资助；LIBREXIA ACS试验在ClinicalTrials.gov的注册号为NCT05754957。）
完整摘要 · 英文原文
BACKGROUND: Patients are at increased risk for recurrent ischemic events after an acute coronary syndrome event. Milvexian, an oral factor XIa inhibitor, may reduce the risk of major adverse clinical events with minimal bleeding risk. METHODS: In this phase 3, randomized, placebo-controlled trial, we evaluated the efficacy and safety of milvexian when added to standard antiplatelet therapy within 7 days after an acute coronary syndrome event. Patients were assigned in a 1:1 ratio to receive oral milvexian (25 mg twice daily) or matched placebo. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or ischemic stroke as evaluated in a time-to-event analysis. The principal safety outcome was Bleeding Academic Research Consortium (BARC) type 3c or 5 bleeding (intracranial or intraocular bleeding that compromises vision or fatal bleeding). RESULTS: After a planned interim analysis that was based on 556 adjudicated efficacy end points, the trial was terminated for futility. A total of 14,194 patients had been enrolled, with 7094 assigned to receive milvexian and 7100 to receive placebo. After a median follow-up of 12.2 months, a primary efficacy outcome event had occurred in 384 patients (5.4%) in the milvexian group and in 365 patients (5.1%) in the placebo group (hazard ratio, 1.05; 95% confidence interval, 0.91 to 1.21; P = 0.50). BARC type 3c or 5 bleeding occurred in 23 patients (0.3%) in the milvexian group and in 22 patients (0.3%) in the placebo group (P = 0.88). CONCLUSIONS: Among patients with a recent acute coronary syndrome event, milvexian did not decrease the risk of cardiovascular death, myocardial infarction, or ischemic stroke but did not increase the risk of intracranial or fatal bleeding, as compared with placebo. (Funded by Janssen Research and Development and Bristol Myers Squibb; LIBREXIA ACS ClinicalTrials.gov number, NCT05754957.).