Allopurinol protective against peripheral arterial disease in elderly
Allopurinol may reduce the risk of peripheral arterial disease (PAD) in the elderly, with the protective effect of the drug increasing as duration of use increases, according to a retrospective cohort study from the US.
Using data from 5 percent of the Medicare beneficiaries (n=25,282) aged ≥65 years without PAD at baseline, researchers identified 26,985 episodes of new allopurinol exposure. Of the episodes, 3,167 (12 percent) ended in incident PAD.
Multivariable Cox regression analysis showed that allopurinol use reduced the risk of incident PAD by 12 percent (hazard ratio [HR], 0.88; 95 percent CI, 0.81 to 0.95). The risk was also associated with female gender (HR, 0.84; 0.78 to 0.90).
The extent of protection of allopurinol against PAD increased with longer durations of use. HRs for PAD were 0.88 (0.79 to 0.97) in the group with 181 days to 2 years of use and 0.75 (0.63 to 0.89) in those with >2 years of use.
Conversely, factors found to be associated with higher PAD risk included older age (age 75 to <85 and ≥85 years), higher Charlson index score and black race.
Sensitivity analyses controlling for cardiac conditions and medications returned similar results, with minimal to no attenuation of HRs.
A common manifestation of atherosclerosis, PAD is a major health problem, especially in the elderly. The disease affects approximately 8.5 million Americans, with the prevalence increasing with age. The mechanism by which allopurinol (commonly used to treat gout) reduces the risk of PAD potentially involves xanthine oxidase, which has long been suspected to play a role in cardiovascular disease. Xanthine oxidase inhibitors, such as allopurinol, demonstrate a dual mechanism of reduction of oxidative stress and urate lowering, which in turn reduce the risk of cardiovascular disease. [Lancet 2013;382:132940; Diabetic Med 2004;21:7249; J Rheumatol 2007;34:18827]