Low-Dose Versus Standard Warfarin After Mechanical Mitral Valve Replacement: A Randomized Controlled Trial.
The Annals of thoracic surgery
washington; seattle; swedish
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 trial assessed the safety and efficacy of warfarin at doses lower than currently recommended, in patients with an On-X 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 to 2.5) or standard-dose warfarin (target INR 2.5 to 3.5). All patients were prescribed aspirin 81 mg daily and encouraged to use home INR testing. The primary endpoint was the sum of the linearized rates of thromboembolism, valve thrombosis, and bleeding events. Secondary endpoints included death, valve-related events, New York Heart Association classification, and valve hemodynamics.
Results: Mean patient follow-up was 4.1 years. Mean INR was 2.47 and 2.92 (P <.001) in the low-dose and standard-dose warfarin groups, respectively. Primary endpoint rates were 11.9%/patient-year in the low-dose group and 12.0%/patient-year in the standard-dose group (P = .97). The -0.07% difference (95% confidence interval: -0.07, -0.06) was noninferior (<1.5% margin). Individual rates (expressed as %/patient-year) of thromboembolism (2.3% vs 2.5%), valve thrombosis (0.5% vs 0.5%), and major bleeding (4.9% vs 4.3%) were also similar and noninferior.
Conclusions: Low-dose warfarin was noninferior to standard-dose warfarin in patients with an On-X mechanical mitral prosthesis, following >3 postoperative months of standard anticoagulation therapy. (PROACT Clinicaltrials.gov number, NCT00291525).
Chu, Michael W A; Ruel, Marc; Graeve, Allen; Gerdisch, Marc W; Damiano, Ralph J; Smith, Robert L; Keeling, William Brent; Wait, Michael A; Hagberg, Robert C; Quinn, Reed D; Sethi, Gulshan K; Floridia, Rosario; Barreiro, Christopher J; Pruitt, Andrew L; Accola, Kevin D; Dagenais, Francois; Markowitz, Alan H; Ye, Jian; Sekela, Michael E; Tsuda, Ryan Y; Duncan, David A; Swistel, Daniel G; Harville, Lacy E; DeRose, Joseph J; Lehr, Eric J; Puskas, John D; and PROACT Mitral Investigators, "Low-Dose Versus Standard Warfarin After Mechanical Mitral Valve Replacement: A Randomized Controlled Trial." (2022). Articles, Abstracts, and Reports. 5838.