Allopurinol for myocardial ischemia

Allopurinol for myocardial ischemia

Allopurinol for myocardial ischemia: The established role of allopurinol, a xanthine oxidase inhibitor is in the treatment of hyperuricemia and gout. Xanthine oxidase being a potent mediator of oxidative stress, allopurinol also reduces tissue oxidative stress. Improvement of myocardial oxidative stress enhances myofilament responsiveness to calcium. This mechanism has been shown to improve myocardial contractile force in animal experimental studies of heart failure. But a clinical study of oxypurinol in symptomatic heart failure patients failed to document benefit [Hare JM, Mangal B, Brown J, et al. Impact of oxypurinol in patients with symptomatic heart failure. Results of the OPT-CHF study. J Am Coll Cardiol 2008;51:2301-2309]. But an important criticism of the study was that the dose was inadequate and so was the duration of follow up. Oxypurinol has also been shown to improve coronary and peripheral endothelial function in patients with coronary artery disease.

Recently, the addition of 600 milligram per day of allopurinol to the treatment regime of those who have stable angina pectoris despite optimal medical management has been shown to increase the median exercise time to ST segment depression and the total exercise time [Noman A et al. Effect of high-dose allopurinol on exercise in patients with chronic stable angina: a randomised, placebo controlled crossover trial Lancet 2010;375:2161-2167]. There was also a slight but significant increase in the maximum rate pressure product. This effect of allopurinol in myocardial ischemia is thought to be due to the abolishing of vascular oxidative stress and improved endothelial dependent vasodilation [Rajendra NS et al. Mechanistic insights into the therapeutic use of high-dose allopurinol in angina pectoris J Am Coll Cardiol 2011;58:820-828].