加拿大汉密尔顿血栓和动脉粥样硬化研究所Jeffrey I. Weitz团队研究了Milvexian预防静脉血栓栓塞的疗效。相关论文于2021年11月15日发表在《新英格兰医学杂志》上。

XIa因子抑制剂用于预防和治疗静脉和动脉血栓栓塞可能比传统抗凝剂更有效，出血更少。关于口服因子XIa抑制剂milvexian的疗效和安全性，还需要更多的数据。

在这一平行组、临床2期试验中，研究组随机分配1242名接受膝关节置换术的患者，分别接受milvexian（25 mg、50 mg、100 mg或200 mg，每日两次；或25 mg、50 mg或200 mg，每日一次）七种术后方案中的一种，或依诺肝素（40 mg，每日一次）治疗。主要疗效结局为静脉血栓栓塞（包括无症状深静脉血栓、经证实的症状性静脉血栓栓塞或全因死亡）。主要的安全性结局是出血。

在每天两次服用milvexian的患者中，服用25 mg的129例患者中有27例（21%）发生静脉血栓栓塞，服用50 mg的124例患者中有14例（11%），服用100 mg的134例患者中有12例（9%），服用200 mg的131例患者中有10例（8%）。在每天服用一次milvexian的患者中，服用25 mg的28名患者中有7名（25%）发生静脉血栓栓塞，服用50 mg的127名患者中有30名（24%），服用200 mg的123名患者中有8名（7%），而服用依诺肝素的252名患者中有54名（21%）。

每日两次服用milvexian的剂量-反应关系显著，每日两次服用milvexian的静脉血栓栓塞发生率为12%，显著低于预先设定的基准30%。923名服用milvexian的患者中有38名（4%）出现严重出血，296名服用依诺肝素的患者中有12名（4%）；主要或临床相关的非重大出血发生率分别为1%和2%；严重不良事件报告率分别为2%和4%。

研究结果表明，对于接受膝关节置换术的患者，口服milvexian抑制因子XIa可有效预防静脉血栓栓塞，且出血风险较低。

附：英文原文

Title: Milvexian for the Prevention of Venous Thromboembolism | NEJM

Author: Jeffrey I. Weitz, M.D.,, John Strony, M.D.,, Walter Ageno, M.D.,, David Gailani, M.D.,, Elaine M. Hylek, M.D.,, Michael R. Lassen, M.D.,, Kenneth W. Mahaffey, M.D.,, Ravi S. Notani, M.B.A.,, Robin Roberts, M.S.,, Annelise Segers, M.D.,, and Gary E. Raskob, Ph.D.

Issue&Volume: 2021-11-15

Abstract:

Background

Factor XIa inhibitors for the prevention and treatment of venous and arterial thromboembolism may be more effective and result in less bleeding than conventional anticoagulants. Additional data are needed regarding the efficacy and safety of milvexian, an oral factor XIa inhibitor.

Methods

In this parallel-group, phase 2 trial, we randomly assigned 1242 patients undergoing knee arthroplasty to receive one of seven postoperative regimens of milvexian (25 mg, 50 mg, 100 mg, or 200 mg twice daily or 25 mg, 50 mg, or 200 mg once daily) or enoxaparin (40 mg once daily). The primary efficacy outcome was venous thromboembolism (which was a composite of asymptomatic deep-vein thrombosis, confirmed symptomatic venous thromboembolism, or death from any cause). The principal safety outcome was bleeding.

Results

Among the patients receiving milvexian twice daily, venous thromboembolism developed in 27 of 129 (21%) taking 25 mg, in 14 of 124 (11%) taking 50 mg, in 12 of 134 (9%) taking 100 mg, and in 10 of 131 (8%) taking 200 mg. Among those receiving milvexian once daily, venous thromboembolism developed in 7 of 28 (25%) taking 25 mg, in 30 of 127 (24%) taking 50 mg, and in 8 of 123 (7%) taking 200 mg, as compared with 54 of 252 patients (21%) taking enoxaparin. The dose–response relationship with twice-daily milvexian was significant (one-sided P<0.001), and the 12% incidence of venous thromboembolism with twice-daily milvexian was significantly lower than the prespecified benchmark of 30% (one-sided P<0.001). Bleeding of any severity occurred in 38 of 923 patients (4%) taking milvexian and in 12 of 296 patients (4%) taking enoxaparin; major or clinically relevant nonmajor bleeding occurred in 1% and 2%, respectively; and serious adverse events were reported in 2% and 4%, respectively.

Conclusions

Postoperative factor XIa inhibition with oral milvexian in patients undergoing knee arthroplasty was effective for the prevention of venous thromboembolism and was associated with a low risk of bleeding.

DOI: 10.1056/NEJMoa2113194

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2113194