Allopurinol as a possible oxygen sparing agent during exercise in peripheral arterial disease

  • Alan Robertson

    Student thesis: Doctoral ThesisDoctor of Medicine


    Patients with peripheral arterial disease (PAD) can only walk so far before they get leg pain (intermittent claudication) and have to stop. They are also at risk in the future of needing amputation of one of their limbs. Allopurinol is a new possible treatment for this condition as it has been shown in coronary arterial disease to prolong exercise before angina pain occurs.

    This is thought to be because allopurinol can both prevent oxygen wastage in tissues and prevent the formation of harmful oxidative stress. We hypothesised that allopurinol could prolong the time to leg pain in participants with PAD.

    In a double-blind, randomised controlled clinical trial 50 participants with PAD were randomised to receive either allopurinol 300mg twice daily or placebo for six months. The primary outcome was change in exercise capacity on treadmill testing at six months. Secondary outcomes were six-minute walking distance, Walking Impairment Questionnaire, SF-36 QoL questionnaire, flow-mediated dilatation and oxidised LDL. Outcome measures were repeated mid-study and at end of study.

    The mean age of participants was 68.4 years (SD 1.2) with 39/50 (78%) male. Only five participants withdrew in the course of the study, two in the active group and three in the placebo group. There was a significant reduction in uric acid levels in those on active treatment of 52.1% (p<0.001), but no significant change in either the pain-free or the maximum distance they were able to walk. 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.

    In summary, 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 following treatment in patients with peripheral arterial disease.
    Date of Award2014
    Original languageEnglish
    SponsorsBritish Heart Foundation
    SupervisorAllan Struthers (Supervisor)


    • Allopurinol
    • Peripheral arterial disease
    • Oxidative stress
    • Exercise testing

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