AXIOMATIC-TKR: Oral Factor Xla Inhibitor For the Prevention of Venous Thromboembolism

Use of the oral factor Xla inhibitor, milvexian, reduced the risk of postoperative thromboembolism in patients undergoing knee arthroplasty in a dose-dependent manner without increasing bleeding risks compared with use of a more conventional anticoagulant, according to findings from AXIOMATIC-TKR presented Nov. 15 during AHA 2021 and simultaneously published in the New England Journal of Medicine. Researchers did note that “further studies are needed to determine whether oral anticoagulants that target factor XIa can dissociate thrombosis from hemostasis.”

The study randomized 1,242 patients undergoing knee arthroplasty to 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 the anticoagulant enoxaparin (40 mg once daily). The primary efficacy outcome was venous thromboembolism, and the primary safety outcome was bleeding.

Results found that in those patients taking 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 on the milvexian once daily regimen, 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. In those assigned enoxaparin, venous thromboembolism occurred in 54 of 252 patients (21%).

According to researchers, 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%. They also noted that bleeding rates of any severity were similar (4%) in those taking milvexian and enoxaparin. Serious adverse events were reported in 2% of patients in the milvexian group compared with 4% in the enoxaparin group.

“This trial provides proof of principle that milvexian is an effective antithrombotic agent,” said Jeffrey Weitz, MD, FACC, and colleagues.

Keywords: AHA Annual Scientific Sessions, American Heart Association, AHA21, Venous Thromboembolism, Anticoagulants


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