Weitz JI, Strony J, Ageno W, et al. - In patients undergoing knee arthroplasty, venous thromboembolism can be effectively prevented by postoperative factor XIa inhibition with oral milvexian and this strategy was related to a low risk of bleeding.

• This parallel-group, phase 2 trial included 1,242 patients undergoing knee arthroplasty who were randomized 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).

• In the milvexian twice daily group, venous thromboembolism occurred in 21% receiving 25 mg, in 11% taking 50 mg, in 9% taking 100 mg, and in 8% taking 200 mg.

• In patients taking milvexian once daily, venous thromboembolism occurred in 25% on 25 mg, in 24% taking 50 mg, and in 7% receiving 200 mg, vs 21% taking enoxaparin.

• Significant dose–response association with twice-daily milvexian was reported, and twice-daily milvexian was linked with 12% incidence of venous thromboembolism, which was significantly lower compared with the prespecified benchmark of 30%.

• In milvexian and enoxaparin groups, bleeding of any severity occurred in 4% and 4%; major or clinically relevant nonmajor bleeding occurred in 1% and 2%, respectively; and serious adverse events occurred in 2% and 4%, respectively.