Among patients with gout, treatment with febuxostat vs allopurinol did not increase the risk for serious cardiovascular-related adverse events or death, according to study results published in Clinical Cardiology.

There are conflicting data on the risk for cardiovascular safety associated with febuxostat. The US Food and Drug Administration (FDA) issued a public safety alert highlighting the discussion of cardiovascular safety of febuxostat; however, the European Medicines Agency (EMA)-required febuxostat vs allopurinol trial showed that febuxostat was not associated with an increased cardiovascular risk.

The objective of the current systematic review and meta-analysis was to determine the adverse cardiovascular events and mortality risks associated with febuxostat.

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Researchers searched clinical trials of febuxostat and allopurinol in the treatment of gout among older patients using PubMed, EMBASE, and the Cochrane Library database from January 2000 to April 2021.

The meta-analysis included 16 clinical trials with 257,851 participants. Median age of the patients who received treatment with febuxostat ranged from 45.5 to 76.0 years, and the median age of patients who received treatment with allopurinol ranged from 65.0 to 76.0 years.

Compared with patients who received allopurinol, those received febuxostat had significantly decreased risks for urgent coronary revascularization (odds ratio [OR], 0.84, 95% CI, 0.77-0.90; P <.0001) and stroke (OR, 0.87, 95% CI, 0.79-0.97; P =.009).

Initiation of febuxostat was not associated with an increased risk for 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).

Subgroup analyses according to age, population and study design showed that febuxostat treatment could significantly reduce the occurrence of stroke among older (≥65 years) patients (OR, 0.88, 95% CI, 0.79–0.99; P =.03), and those who were White (OR, 0.88, 95% CI, 0.79-0.99; P =.04). Febuxostat was also shown to reduce the incidence of nonfatal myocardial infarction in White participants (OR, 0.87, 95% CI, 0.79–0.96; P =.007). No significant differences in cardiovascular related mortality and all-cause mortality were observed across the subgroups.

The study had several limitations, including the relatively small number of women included in the studies and differences between included studies in the inclusion criteria, treatment period, and follow-up period.

“[O]ur meta-analysis suggested that febuxostat users did not significantly increase the risk [for] cardiovascular events or all-cause mortality compared with allopurinol users. However, more high-quality, double-blinded, large, randomized studies are needed to elucidate this issue,” the researchers concluded.


Gao L, Wang B, Pan Y, Lu Y, Cheng R. Cardiovascular safety of febuxostat compared to allopurinol for the treatment of gout: A systematic and meta-analysis. Clin Cardiol. Published online May 20, 2021. doi:10.1002/clc.23643

This article originally appeared on Rheumatology Advisor