Background Recently we found that use of allopurinol, the most commonly used urate-lowering therapy (ULT), was associated with a reduction of the risk of myocardial infarction and stroke, acute manifestations of CAD. Given that both PAD and CAD are manifestations of atherosclerosis and a similarity of disease pathophysiology between them, an obvious question was whether allopurinol use would reduce PAD. To our knowledge, no previous studies have examined whether allopurinol use reduces the risk of PAD.
Objectives To examine whether new allopurinol use is independently associated with a reduction of the risk of incident peripheral arterial disease (PAD) in the U.S. elderly.
Methods We used the 5% random Medicare sample from 2006–2012 to examine the association of allopurinol use and its duration with risk/hazard of incident PAD, in a retrospective cohort study. Multivariable Cox regression models adjusted for demographics, comorbidity, cardiac medications and cardiac conditions. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated.
Results We identified 26,985 episodes of incident allopurinol use in 25,282 beneficiaries, of which 3,167 allopurinol use episodes (12%) ended in incident PAD. In multivariable-adjusted analyses, allopurinol use was associated with HR of 0.88 (95% CI, 0.81, 0.95) for incident PAD, as was female gender, 0.84 (95% CI, 0.78, 0.90). In a separate multivariable-adjusted model, compared no allopurinol use, longer durations of allopurinol use were associated with lower HR of PAD: 181 days to 2 years, 0.88 (95% CI, 0.79, 0.97) and >2 years, 0.75 (95% CI, 0.63, 0.89). Other factors significantly associated with a higher hazard of PAD were age 75-<85 and ≥85, female gender, higher Charlson index score, and black race. Sensitivity analyses adjusting for cardiac conditions and medications, confirmed these findings with minimal to no attenuation of hazard ratios.
Conclusions New allopurinol use was independently associated with a lower risk of PAD in the elderly. Longer allopurinol use durations seemed more protective. Mechanisms of protective effect need to be studied in future studies.
Disclosure of Interest J. Singh Grant/research support from: Takeda and Savient, Consultant for: Savient, Takeda, Regeneron, Merz, Iroko, Bioiberica, Crealta and Allergan pharmaceuticals, WebMD, UBM LLC and the American College of Rheumatology, J. Cleveland: None declared