Urate-Lowering Therapy for Gout May Have Cardiovascular Benefits

Can urate-lowering therapy for gout also reduce cardiovascular risk and mortality?

Gout is the most common inflammatory disorder in developed countries, and it increases the risk of cardiovascular disease. The cornerstone of therapy is urate-lowering medication, such as allopurinol.

Researchers, clinicians, and patients have all wondered about allopurinol’s potential ability to reduce cardiovascular risk and mortality. To date, the few studies that have looked at this hypothesis have offered just a few pointed answers. They have shown that urate-lowering therapy decreases cardiovascular events in chronic kidney disease patients and improves exercise tolerance in angina patients without hyperuricemia, but what about other populations?

A team of researchers investigated allopurinol’s effects in terms of cardiovascular outcomes and all-cause mortality in a new study published in the March 2016 issue of The American Journal of Medicine. They identified 7127 hyperuricemic (>6 mg/dL) patients receiving allopurinol over an 18-year period and a control cohort of 7127 participants who had gout but did not take allopurinol. This control group was matched for age, sex, and follow-up length.

This Danish study excluded patients who had had cancer within the previous 5 years or had taken any urate-lowering therapy other than allopurinol in the past 5 years. Allopurinol is only prescribed as secondary prophylaxis after a gouty flare in Denmark, so the patients in this study were more likely to have inflammatory flares than those in other countries with comparable urate levels.

The study authors found that allopurinol decreased the incidence of major cardiovascular events (defined as the composite of myocardial infarction, stroke, and cardiovascular death) by 11% and all-cause mortality by 32%. Younger patients and those with lower urate concentrations tended to benefit most from treatment, but this was a tendency and not a significant finding.

These findings conflict with those from a Taiwanese study, but observational studies from 2010 and 2009 support allopurinol’s all-cause mortality benefit.

The current study's strengths include the use of comprehensive medical records detailing admissions, outpatient visits, prescription data, causes of death, and all blood samples. A weakness is that the researchers were unable to track smoking status.

This study highlights the importance of prescribing allopurinol in hyperuricemic patients to reduce cardiovascular risk. Health care providers should keep in mind that nonadherence and undertreatment is a common problem among gout patients, so they should consider prescribing allopurinol more widely to hyperuricemic patients and counseling on the importance of adherence.