A Higher-Than-Standard-Intensity International Normalized Ratio Goal for Patients Undergoing Mechanical Aortic Valve Replacement With Additional Thrombotic Risk Factors: Protocol for a Systematic Review and Meta-Analysis

BACKGROUND: Lifelong anticoagulation therapy with vitamin K antagonists is recommended following mechanical aortic valve replacement (MAVR) to prevent valve thrombosis. Current guidelines recommend a standard international normalized ratio (INR) of 2.5 for patients with MAVR without additional thromboembolic risk factors, and a higher INR goal of 3.0 for those with conditions such as atrial fibrillation, prior thromboembolism, or left ventricular dysfunction. However, limited clinical evidence exists to guide anticoagulation intensity in this high-risk subgroup, necessitating a systematic review. OBJECTIVE: We aimed to assess the safety and efficacy of higher-intensity INR goals (>3.0) compared to standard-intensity goals (approximately 2.5) in patients with MAVR with additional thromboembolic risk factors. METHODS: This protocol describes a systematic review and meta-analysis following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. A comprehensive literature search will be conducted across PubMed, Embase, and the Cochrane Library for studies published before December 18, 2024. Eligible studies include randomized controlled trials (RCTs), cohort studies, and follow-up studies involving adult patients with MAVR on warfarin therapy, stratified by the presence of additional thromboembolic risk factors. Non-English-language studies, case reports, editorials, and animal studies will be excluded. RESULTS: The review will synthesize existing data to compare the risks and benefits of intensified anticoagulation in patients with MAVR with additional thromboembolic risk factors. Data analysis and manuscript preparation are scheduled for July-August 2025. CONCLUSIONS: This study will provide critical evidence on INR management in high-risk patients with MAVR, potentially informing future updates to clinical guidelines and optimizing the balance between thromboembolic prevention and bleeding risk. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/73389.