Risk of Major Adverse Cardiovascular Events in Patients Treated with Febuxostat Compared to Allopurinol: A Systematic Review and Meta-Analysis

INTRODUCTION: To evaluate the cardiovascular safety of febuxostat compared to allopurinol in patients with gout or hyperuricemia, with a focus on Major Adverse Cardiovascular Event (MACE) outcomes. METHODS: PubMed and Scopus databases were searched for studies published up to 25 September 2025. Randomized Controlled Trials (RCTs) and observational cohort studies were included comparing febuxostat and allopurinol in patients with gout or hyperuricemia and reporting cardiovascular outcomes. Study selection, data extraction, and methodological quality assessment were performed using PRISMA guidelines by independent reviewers. A random-effects meta-analysis was performed to estimate hazard ratios with 95% confidence intervals for MACE and other cardiovascular events. RESULT: A total of eleven studies encompassing 3,559,863 participants were included. Pooled estimates demonstrated no statistically significant difference between febuxostat and allopurinol in terms of MACE risk. Similarly, no significant differences were observed for myocardial infarction (HR 1.17; 95% CI 0.85-1.63), cardiovascular mortality (HR 1.01; 95% CI 0.59-1.72), congestive heart failure (HR 1.05; 95% CI 0.71-1.55), or cerebrovascular events (HR 0.82; 95% CI 0.54-1.25). Substantial heterogeneity was noted across several outcome measures. DISCUSSION: The findings of this study are consistent with large randomized trials and observational studies demonstrating non-inferiority of febuxostat to allopurinol across major cardiovascular endpoints. Substantial heterogeneity across several outcomes reflects variation in study design, population characteristics, and follow-up duration. CONCLUSION: This review showed no significant differences between the two therapies across major cardiovascular endpoints.