Cardiovascular Outcomes of Uric Acid Lowering Medications: A Meta-Analysis

Although hyperuricemia is a recognized risk factor for cardiovascular diseases, mixed results have been reported regarding the associations between uric acid-lowering medications and cardiovascular events. This meta-analysis compared the cardiovascular outcomes of different uric acid-lowering medications and placebo.

Following PRISMA guidelines, we searched OVID Medline, Embase, Web of Science, and Cochrane databases to identify potentially relevant articles until December 2023. Studies must be randomized or observational, report cardiovascular and mortality outcomes, and compare uric acid-lowering medications to placebo or each other. Data was analyzed using Revman (version 5.4) software.

A total of 3,393 studies were searched, after which 47 studies were included, totaling 3,803,509 patients (28 studies comparing xanthine oxidase inhibitors (XOI) versus placebo, 17 studies comparing allopurinol and febuxostat, and 2 studies comparing XOI and uricosuric agents). Overall mean age was 57.3 years, and females comprised 20.8% of all studies. There were no significant differences between XOI and placebo for cardiovascular outcomes (mortality, myocardial infarction, major adverse cardiovascular events, heart failure, or arrhythmia). There was significant heterogeneity in all these pooled analyses. Comparing Allopurinol to Febuxostat, there was a lower risk of heart failure in febuxostat than allopurinol in 3 RCTs (OR 0.66, 95% CI 0.50-0.89, p = 0.006). Other cardiovascular outcomes were not different. Lastly, when comparing XOI and uricosuric agents, no significant differences in MI rates were evident.

XOI was not associated with reduced cardiovascular events compared to placebo. When comparing XOI agents, Febuxostat might reduce the risk of HF, but future studies are required to confirm the findings from the current study.