A Randomized Controlled Trial of Allopurinol in Patients With 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.
Division of Cardiovascular and Diabetes Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom. Electronic address: alanrobertson@nhs.net.
Alan J
AJ
Robertson
Division of Cardiovascular and Diabetes Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom.
Allan D
AD
Struthers
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D016166:Free Radical Scavengers / Q000008:administration & dosage; D006801:Humans; D007383:Intermittent Claudication / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000188:drug therapy; D012189:Retrospective Studies; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D016138:Walking / Q000502:physiology*
D016166:Free Radical Scavengers; D000493:Allopurinol