Low-Dose vs Standard Warfarin After Mechanical Mitral Valve Replacement: A Randomized Trial
Document Type
Article
Publication Date
4-1-2023
Institution/Department
Cardiology, Surgery, Pharmacy
Journal Title
The Annals of Thoracic Surgery
MeSH Headings
Humans; Warfarin (adverse effects); Anticoagulants (adverse effects); Prospective Studies; Mitral Valve (surgery); Thromboembolism (etiology, prevention & control); Hemorrhage (etiology); Thrombosis (etiology); Heart Valve Prosthesis Implantation (adverse effects)
Abstract
BACKGROUND: Current guidelines recommend a target international normalized ratio (INR) range of 2.5 to 3.5 in patients with a mechanical mitral prosthesis. The Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT) Mitral randomized controlled noninferiority trial assessed safety and efficacy of warfarin at doses lower than currently recommended in patients with an On-X (Artivion, Inc) mechanical mitral valve. METHODS: After On-X mechanical mitral valve replacement, followed by at least 3 months of standard anticoagulation, 401 patients at 44 North American centers were randomized to low-dose warfarin (target INR, 2.0-2.5) or standard-dose warfarin (target INR, 2.5-3.5). All patients were prescribed aspirin, 81 mg daily, and encouraged to use home INR testing. The primary end point was the sum of the linearized rates of thromboembolism, valve thrombosis, and bleeding events. The design was based on an expected 7.3% event rate and 1.5% noninferiority margin. RESULTS: Mean patient follow-up was 4.1 years. Mean INR was 2.47 and 2.92 (P 1.5%, thus noninferiority was not achieved. Rates (percentage per patient-year) of the individual components of the primary end point were 2.3% vs 2.5% for thromboembolism, 0.5% vs 0.5% for valve thrombosis, and 9.13% vs 9.04% for bleeding. CONCLUSIONS: Compared with standard-dose warfarin, low-dose warfarin did not achieve noninferiority for the composite primary end point. (PROACT Clinicaltrials.gov number, NCT00291525).
First Page
929
Last Page
938
Recommended Citation
Chu MWA, Ruel M, Graeve A, et al. Low-Dose vs Standard Warfarin After Mechanical Mitral Valve Replacement: A Randomized Trial. Ann Thorac Surg. 2023;115(4):929-938. doi:10.1016/j.athoracsur.2022.12.031
