Effects of Febuxostat on Mortality and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

OBJECTIVE: To investigate the association between using febuxostat and cardiovascular events. METHODS: Systematic search of randomized controlled trials was performed using PubMed/MEDLINE, Cochrane review, and EMBASE databases through April 17, 2019. Meta-analysis was performed using random effect model and estimates were reported as risk difference (RD) with 95% CIs. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. The main outcomes of interest were cardiovascular mortality and all-cause mortality. RESULTS: A total of 15 randomized controlled trials (16,070 participants) were included. The mean ± SD age was 58.1±11.7 years. At the median follow-up of 6.4 months, use of febuxostat was not associated with statistically significant risk of cardiovascular mortality (RD, 0.12%; 95% CI, -0.25% to 0.49%; I(2)=48%; low certainty evidence), all-cause mortality (RD, 0.20%; 95% CI, -0.28% to 0.68%; I(2) =60%; very low certainty evidence), major adverse cardiovascular events (RD, 0.40%; 95% CI, -0.34% to 1.13%; I(2)=26%; low certainty evidence), myocardial infarction (RD, -0.06%; 95% CI, -0.29% to 0.17%; I(2) =0%; moderate certainty evidence), stroke (RD, 0.10%; 95% CI, -0.15% to 0.35%; I(2)=0%; moderate certainty evidence), or new-onset hypertension (RD, 1.58%; 95% CI, -0.63% to 3.78%; I(2)=58%; very low certainty evidence). These findings were consistent in patients with existing cardiovascular disease. CONCLUSION: This meta-analysis suggested that use of febuxostat was not associated with higher risk of mortality or adverse cardiovascular outcomes in patients with gout and hyperuricemia. The results were limited by low to moderate certainty of evidence.