allopurinol and Peripheral-Arterial-Disease

Patients with peripheral arterial disease (PAD) are limited by intermittent claudication in the distance they can walk. Allopurinol has been shown in coronary arterial disease to prolong exercise before angina occurs, likely by prevention of oxygen wastage in tissues and reduction of harmful oxidative stress.. In this study we evaluated whether allopurinol could prolong the time to development of leg pain in participants with PAD. In a double-blind, randomized controlled clinical trial participants were randomized to receive either allopurinol 300 mg twice daily or placebo for 6 months. The primary outcome was change in exercise capacity on treadmill testing at 6 months. Secondary outcomes were 6-minute walking distance, Walking Impairment Questionnaire, SF-36 questionnaire, flow-mediated dilatation, and oxidized low-density lipoprotein. Outcome measures were repeated midstudy and at the end of study. The mean age of the 50 participants was 68.4 ± 1.2 years with 39 of 50 (78%) male.. Five participants withdrew during the study (2 active, 3 placebo). There was a significant reduction in uric acid levels in those who received active treatment of 52.1% (P < 0.001), but no significant change in either the pain-free or the maximum walking distance. Other measures of exercise capacity, blood vessel function, and the participants' own assessment of their health and walking ability also did not change during the course of the study.. Although allopurinol has been shown to be of benefit in a number of other diseases, in this study there was no evidence of any improvement after treatment in patients with PAD.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Dose-Response Relationship, Drug; Double-Blind Method; Exercise Test; Exercise Tolerance; Female; Follow-Up Studies; Free Radical Scavengers; Humans; Intermittent Claudication; Male; Middle Aged; Peripheral Arterial Disease; Retrospective Studies; Surveys and Questionnaires; Treatment Outcome; Walking

The aim was to examine whether allopurinol use is independently associated with a reduction in the risk of incident peripheral arterial disease (PAD) in the US elderly.. We used the 5% random Medicare sample from 2006 to 2012 to examine the association of allopurinol use and duration of use with the risk or hazard of incident PAD in a retrospective cohort study using a new user design. Multivariable Cox regression models adjusted for demographics, co-morbidity, cardiac medications and cardiac conditions. Hazard ratios (HRs) and 95% CIs were calculated.. We identified 26 985 episodes of incident allopurinol use in 25 282 beneficiaries; 3167 allopurinol use episodes (12%) ended in incident PAD. In multivariable-adjusted analyses, allopurinol use was associated with an HR of 0.88 (95% CI: 0.81, 0.95) for incident PAD, as was female gender, HR 0.84 (95% CI: 0.78, 0.90). In a separate multivariable-adjusted model, compared with 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 HR of PAD were age 75 to < 85 and ⩾85 years, higher Charlson index score and black race. Sensitivity analyses that adjusted for cardiac conditions and medications confirmed these findings, with minimal to no attenuation of HRs.. New allopurinol use was independently associated with a lower risk of PAD in the elderly. Longer allopurinol use durations seemed more protective. Mechanisms of the protective effect need to be investigated in future studies.

Topics: Age Factors; Aged; Aged, 80 and over; Allopurinol; Antirheumatic Agents; Drug Prescriptions; Female; Humans; Incidence; Male; Medicare; Multivariate Analysis; Peripheral Arterial Disease; Proportional Hazards Models; Regression Analysis; Retrospective Studies; Risk Factors; Sex Factors; Time Factors; United States