Cardiovascular safety of febuxostat compared to allopurinol for the treatment of gout: A systematic and meta‐analysis

The cardiovascular safety of febuxostat compared to allopurinol for the treatment of gout remains equivocal. Febuxostat had a better safety outcome compared with allopurinol. In this systematic review and meta‐analysis, we searched MEDLINE and Embase for articles published between March 1, 2000 and April 4, 2021, without any language restrictions. We did a systematic review and meta‐analysis of included clinical trials to evaluate the cardiovascular safety of febuxostat compared to allopurinol for treatment of chronic gout. Two reviewers independently selected studies, assessed study quality, and extracted data. Risk ratios were calculated with random effects and were reported with corresponding 95% confidence intervals (CI). From 240 potentially relevant citations, 224 papers were excluded; 16 studies were ultimately included in the analysis. Febuxostat had a better safety outcome compared with allopurinol，which was the composite of urgent coronary revascularization (OR: 0.84, 95% CI: 0.77–0.90, p < .0001) and stroke (OR: 0.87, 95% CI: 0.79–0.97, p = .009). However, that difference was not found in nonfatal myocardial infarction (OR: 0.99, 95% CI: 0.80–1.22, p = .91), cardiovascular related mortality (OR: 0.98, 95% CI: 0.69–1.38, p = .89) and all‐cause mortality (OR: 0.93, 95% CI: 0.75–1.15, p = .52). No significant differences in cardiovascular related mortality and all‐cause mortality were observed across any subgroup. This meta‐analysis adds new evidence regarding the cardiovascular safety of febuxostat in patients. Initiation of febuxostat in patients was not associated with an increased risk of death or serious cardiovascular related adverse events compared with allopurinol.