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HomeHaematologyOral milvexian for prevention of venous thromboembolism — McMaster University

Oral milvexian for prevention of venous thromboembolism — McMaster University

Oral milvexian in patients undergoing knee arthroplasty was effective for the prevention of venous thromboembolism and was associated with a low risk of bleeding. The study was published in the New England Journal of Medicine and presented at a late-breaking session at the 2021 American Heart Association Scientific Sessions.

Milvexian is unique in that it works by targeting factor XIa, a clotting enzyme that causes dangerous thrombosis and blood clots, but is not vital for stopping bleeding from injuries.

Researchers compared milvexian with enoxaparin for prevention of blood clots in 1,242 patients from 18 countries undergoing knee replacement surgery, who were enrolled between June 2019 and February 2021.

They found that at a total daily dose of 100mg or more, milvexian resulted in better clot protection but no increase in bleeding compared with enoxaparin, the control drug. Milvexian was evaluated in daily doses ranging from 25 to 400mg; there was no increase in bleeding over this wide range of doses.

“The major side effect of current oral anti-clotting drugs is bleeding, and the fear of bleeding leads to their underuse. This sets the need for safer oral anticoagulants, which is where milvexian comes in," said senior author Jeffrey Weitz, a professor of medicine and biochemistry and biomedical sciences at McMaster University. He is also the executive director of the Thrombosis and Atherosclerosis Research Institute of McMaster and Hamilton Health Sciences.

“Blood clots are responsible for one in four deaths worldwide. Anticoagulants (blood thinners) are a mainstay for the treatment and prevention of clots in veins and arteries and we urgently need safer oral medications to reduce the burden from what are often lifelong conditions.”

Weitz said that blood clots are the underlying cause of heart attack, stroke, deep vein thrombosis, and pulmonary embolism. Many of these conditions require lifelong anticoagulant treatment. So there is a need for safer oral anticoagulants like milvexian.

He said the study focused on patients undergoing knee replacement surgery because they are at high risk for postoperative blood clots, and such clots can be readily identified with venograms, X-rays of the leg veins. This patient population therefore provides an ideal testing ground for new anticoagulants, because effective and safe doses can be identified.

Weitz said his milvexian study is the first of several investigations of oral factor XIa inhibitors. The results of the other studies will probably be released next year.

Study details
Milvexian for the Prevention of Venous Thromboembolism

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

Published in the New England Journal of Medicine on 15 November 2021

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.

 

NEJM abstract – Milvexian for the Prevention of Venous Thromboembolism (Open access)

 

See more from MedicalBrief archives:

 

Single-shot abelacimab cuts venous thromboembolism risk in knee surgery

 

Adequate compression therapy cuts complication risk in DVT

 

Tall people more likely to develop blood clots

 

Thrombus formation varies according to the type of drug

 

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