VANCOUVER, British Columbia, Canada—Gouty arthritis patients who take allopurinol live longer than those who do not, and the survival benefit is comparable to that associated with major cardiovascular drugs, according to a new study published on-line ahead of print in Rheumatology.¹

“This is the first study to show a survival benefit of allopurinol,” conclude the researchers who were led by Andrew J. Luk, MD, MPH, a rheumatologist at the University of Washington in Seattle. “The magnitude of risk reduction is comparable to that of established cardiovascular drugs, such as ACE inhibitors, Angiotensin II Receptor Blockers and beta-blockers.”

Mechanism of gout survival benefit unclear, might involve heart function

Exactly how treatment with allopurinol saves lives is not fully understood. “It remains unclear if the survival benefit is entirely due to the urate-lowering effect of allopurinol or to other beneficial effects of the drug,” the researchers write. “For example, the effect of allopurinol or its metabolite oxypurinol on cardiovascular function has been tested in a number of studies.”

In the new study of 9,924 veterans with gout who had serum urate levels of  >416 µmol/l (7.0 mg/dl), 1,021 died during follow-up. The gouty arthritis patients treated with allopurinol had higher mortality risk profiles than their counterparts who did not receive allopurinol. This was largely due to cardiovascular risk factors. Veterans treated with allopurinol had a 23% lower mortality rate than those individuals who were not treated with the urate-lowering therapy. The findings held even after the researchers controlled for age, sex, race, body mass index, comorbidities, healthcare utilization, use of cardiovascular and other therapies, blood levels of urate, cholesterol, albumin, and glomerular filtration rate.

Information on the precise causes of death of study participants was not available, but cardiovascular causes are suspected. “Because the excess mortality risk observed among gout patients was due to increased cardiovascular death, the potential survival benefit due to allopurinol would likely come from preventing excess cardiovascular death.”

Patients who received allopurinol showed an average decrease of  –111 µmol/l (–1.86 mg/dl) in their serum urate levels. Allopurinol users had a 40 µmol/l (0.68 mg/dl) lower follow-up serum urate value than controls after the researchers adjusted for baseline blood uric acid levels, the study showed.

Allopurinol and gout survival: Translating research into practice

Calling the findings “encouraging,” the researchers note that it is too early to call for the use of allopurinol to stave off heart disease in gout patients. “Nonetheless, our findings provide justification for further prospective studies of urate-lowering therapy for the prevention of premature death in hyperuricaemic patients.”

“It’s a very interesting paper,” said Herbert S. B. Baraf, MD, the medical director of the Center for Rheumatology and Bone Research, a practicing rheumatologist in Wheaton, Maryland, and a clinical professor of medicine at George Washington University Medical Center in Washington, DC. “If borne out, it would speak volumes about the need to treat asymptomatic hyperuricemia.”

References

1. Luk AJ, Levin GP, Moore EE, et al. Allopurinol and mortality in hyperuricaemic patients. Rheumatology. 2009; [epub ahead of print May 15, 2009].