Compared with benzbromarone, allopurinol was associated with an increased risk for cardiovascular events and all-cause mortality, according to results of a large population-based cohort study published in European Heart Journal.

Patients with gout have a higher risk for cardiovascular disease morbidity and mortality; however, the cardiovascular safety of the medications used to treat gout is not yet clear. Although not approved in the United States, benzbromarone is used treat gout in Asia, some European countries, and South America. 

Researchers of the current study compared the cardiovascular risk between allopurinol and benzbromarone in patients with gout.

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Patients with gout who were new users of allopurinol or benzbromarone were identified using the 2002 to 2017 Korea National Health Insurance Service database. Participants were propensity-score matched in a 5:1 ratio.

The primary endpoint was a composite cardiovascular event of hospitalized myocardial infarction, stroke, transient ischemic attack, or coronary revascularization. Secondary endpoints included cardiovascular and all-cause mortality.

The final cohort included 124,434 patients, of whom 103,695 were initiated with allopurinol and 20,739 with benzbromarone. The most common daily dose index of allopurinol and benzbromarone was 300 mg (35.5%) and 50 mg (46.5%), respectively.

The incidence rate of a composite cardiovascular event was higher in patients who received allopurinol vs benzbromarone (1.81 vs 1.61 per 100 person-years, respectively). The hazard ratio (HR) for all-cause mortality was higher for allopurinol vs benzbromarone (HR, 1.66; 95% CI, 1.43-1.93), though the researchers were not able to identify a mechanism for this finding.

Overall, the risk for death was similar between the 2 treatment groups. The main causes of mortality were diseases of the circulatory system, neoplasm, diseases of the genitourinary system, metabolic diseases, and injury/poisoning.

A limitation of the study was residual or unmeasured confounding due to cohort study design.

The researchers concluded, “In this large population-based cohort study, we found that allopurinol use was associated with an increased risk of nonfatal [cardiovascular] events and all-cause mortality compared [with] benzbromarone. Benzbromarone may reduce [cardiovascular] risk and mortality in patients with gout, although more studies are necessary to confirm our findings and advance the understanding of the biological mechanisms.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures.


Kang EH, Park EH, Shin A, Song JS, Kim SC. Cardiovascular risk associated with allopurinol vs. benzbromarone in patients with gout. Eur Heart J. Published online September 11, 2021. doi:10.1093/eurheartj/ehab619

This article originally appeared on Rheumatology Advisor