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

Abstract

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.

Cardiovascular safety of febuxostat and allopurinol in patients with gout: A meta-analysis

“…In addition to the two randomized controlled trials, there exist other studies about the cardiovascular safety of febuxostat and allopurinol, and the conclusions are also inconsistent. Above all, our conclusion is consistent with that of one network metaanalysis (Zhang et al, 2021), three systematic meta-analyses (Liu et al, 2019;Barrientos-Regala et al, 2020;Gao et al, 2021), and two cohort studies (Chen et al, 2019;Kang et al, 2019). However, our findings are inconsistent with those of one cohort study in the real world (Su et al, 2019).…”

Cardiological and rheumatological expert statement on the management of asymptomatic hyperuricemia in patients at high cardiovascular risk

“…On the one hand, the most recent comparative meta-analyses of allopurinol and febuxostat do not corroborate such data [82][83][84]. On the other, however, single meta--analyses still report results showing a marginally higher risk of CV events when using febuxostat, with no such risk being observed with allopurinol.…”

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

“…Moreover, combining RCTs and cohort studies in meta‐analysis as done in this article was inappropriate because different study designs and comparison groups may lead to high methodological variability or heterogeneity between studies. 3 Gao et al 1 documented that febuxostat had a lower risk of urgent coronary revascularization and stroke compared with allopurinol. The outcome was inconsistent in our meta‐analysis including RCTs, but similar to our meta‐analysis included cohort studies (Table 1 ).…”

“…To the Editor, We read with interest the systematic review and meta-analysis by Gao et al 1 published in the May 2021 issue of Clinical Cardiology. If febuxostat leads to a higher risk of cardiovascular events as compared to allopurinol are debatable.…”