Key result
Oral milvexian reduces postoperative venous thromboembolism to ~12% without increasing bleeding risk vs enoxaparin.
Why the study?
Additional data were needed regarding the efficacy and safety of the oral factor XIa inhibitor milvexian for the prevention and treatment of thromboembolism.
Does postoperative milvexian prevent venous thromboembolism in patients undergoing knee arthroplasty?
RCT (n=1,242)
Open-label for treatment assignment (milvexian vs enoxaparin), blinded to milvexian dose regimen and blinded outcome adjudication
Parallel-group, adaptive design
Yes
Does postoperative milvexian prevent venous thromboembolism in patients undergoing knee arthroplasty?
Absolute Event Rate: 12% vs 30%
p-value: p=<0.001
Postoperative factor XIa inhibition with oral milvexian effectively prevents venous thromboembolism after knee arthroplasty with a bleeding risk comparable to enoxaparin.
Supports oral milvexian for VTE prevention after knee arthroplasty with bleeding risk similar to enoxaparin; extends factor XIa inhibition as an oral option.
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. (Funded by Bristol Myers Squibb and Janssen Research and Development; AXIOMATIC-TKR ClinicalTrials.gov number, NCT03891524.).
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Weitz et al. (2021) conducted an RCT in Venous thromboembolism after elective knee arthroplasty (n=1,242). Milvexian vs. Enoxaparin (40 mg once daily) or prespecified benchmark of 30% was evaluated on Composite of asymptomatic deep-vein thrombosis, confirmed symptomatic venous thromboembolism, or death from any cause (p=<0.001). Postoperative oral milvexian prevented venous thromboembolism in a dose-dependent manner (12% incidence with combined twice-daily regimens vs. prespecified 30% benchmark, P<0.001) without increasing bleeding risk compared to enoxaparin.
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