Accepted for/Published in: JMIR Research Protocols
Date Submitted: Mar 21, 2025
Open Peer Review Period: Mar 24, 2025 - May 19, 2025
Date Accepted: May 29, 2025
(closed for review but you can still tweet)
Does a Higher than Standard-Intensity International Normalized Ratio Goal Benefit Patients Undergoing Mechanical Aortic Valve Replacement with Additional Thrombotic Risk Factors? A Protocol for Systematic Review and Meta-analysis
ABSTRACT
Background:
Lifelong anticoagulation with vitamin K antagonists (VKAs) 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 MAVR patients 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:
To assess the safety and efficacy of higher-intensity INR goals (>3.0) compared to standard-intensity goals (≈2.5) in MAVR patients with additional thromboembolic risk factors.
Methods:
This protocol describes a systematic review and meta-analysis following PRISMA 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 MAVR patients on Warfarin therapy, stratified by the presence of additional thromboembolic risk factors. Non-English studies, case reports, editorials, and animal studies will be excluded. Two independent reviewers will conduct screening and full-text assessment using a PECOS-based framework. Data extraction will be performed in duplicate using a standardized form. Risk of bias will be assessed using the National Heart, Lung, and Blood Institute (NHLBI) tools. Statistical analyses will include pooled risk ratios (RRs) and odds ratios (ORs) for dichotomous outcomes (bleeding, thromboembolic events, mortality) and mean differences for continuous variables, using a random-effects model. Heterogeneity will be assessed via the I² statistic, and subgroup/sensitivity analyses will explore sources of variability. Funnel plots and Egger’s test will assess publication bias.
Results:
The review will synthesize existing data to compare the risks and benefits of intensified anticoagulation in MAVR patients 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 MAVR patients, potentially informing future updates to clinical guidelines and optimizing the balance between thromboembolic prevention and bleeding risk. Clinical Trial: CRD42025639037
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