• Peter Verhamme, B Alexander Yi, Annelise Segers, Janeen Salter, Daniel Bloomfield, Harry R Büller, Gary E Raskob, Jeffrey I Weitz, and ANT-005 TKA Investigators.
• From KU Leuven Department of Cardiovascular Sciences, Vascular Medicine and Hemostasis, Leuven, Belgium (P.V.); Anthos Therapeutics, Cambridge, MA (B.A.Y., J.S., D.B.); International Trial Expertise Advisory and Services (A.S.) and the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam (H.R.B.) - both in Amsterdam; Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.); and the Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada (J.I.W.).
• N. Engl. J. Med. 2021 Aug 12; 385 (7): 609-617.

BackgroundThe role of factor XI in the pathogenesis of postoperative venous thromboembolism is uncertain. Abelacimab is a monoclonal antibody that binds to factor XI and locks it in the zymogen (inactive precursor) conformation.MethodsIn this open-label, parallel-group trial, we randomly assigned 412 patients who were undergoing total knee arthroplasty to receive one of three regimens of abelacimab (30 mg, 75 mg, or 150 mg) administered postoperatively in a single intravenous dose or to receive 40 mg of enoxaparin administered subcutaneously once daily. The primary efficacy outcome was venous thromboembolism, detected by mandatory venography of the leg involved in the operation or objective confirmation of symptomatic events. The principal safety outcome was a composite of major or clinically relevant nonmajor bleeding up to 30 days after surgery.ResultsVenous thromboembolism occurred in 13 of 102 patients (13%) in the 30-mg abelacimab group, 5 of 99 patients (5%) in the 75-mg abelacimab group, and 4 of 98 patients (4%) in the 150-mg abelacimab group, as compared with 22 of 101 patients (22%) in the enoxaparin group. The 30-mg abelacimab regimen was noninferior to enoxaparin, and the 75-mg and 150-mg abelacimab regimens were superior to enoxaparin (P<0.001). Bleeding occurred in 2%, 2%, and none of the patients in the 30-mg, 75-mg, and 150-mg abelacimab groups, respectively, and in none of the patients in the enoxaparin group.ConclusionsThis trial showed that factor XI is important for the development of postoperative venous thromboembolism. Factor XI inhibition with a single intravenous dose of abelacimab after total knee arthroplasty was effective for the prevention of venous thromboembolism and was associated with a low risk of bleeding. (Funded by Anthos Therapeutics; ANT-005 TKA EudraCT number, 2019-003756-37.).Copyright © 2021 Massachusetts Medical Society.

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