Allopurinol raised ischemic threshold by 44% (531.1s vs 369.9s; p=0.027) and reduced nitrate use (87.5% vs 53.8%; p=0.044) but did not improve exercise time in refractory angina.
Does allopurinol improve exercise capacity in patients with refractory angina?
In patients with refractory angina, allopurinol did not improve total exercise duration, although it was associated with a higher ischemic threshold and reduced short-acting nitrate use.
Abstract Introduction Allopurinol has been considered as a therapeutic option for patients with coronary artery disease (CAD) who remain symptomatic despite optimisation of clinical treatment and with no more revascularization possibilities. The two main mechanisms explaining the potential benefit are the reduction of oxidative stress and improvement in endothelial function. However, the role of allopurinol in the management of patients with refractory angina remains unknown. Objectives To assess the efficacy and safety of allopurinol in improving exercise capacity in patients with refractory angina. Methods A prospective, randomized, placebo-controlled, double-blind study, including patients over 18 years of age with a diagnosis of stable angina, as classified by the Canadian Cardiovascular Society (CCS) grading of angina ≥ 2 for at least 3 months, secondary to obstructive CAD confirmed by invasive coronary angiography, taking at least three classes of antianginal drugs, and with documented ischemia. Patients were randomized to receive allopurinol 300 mg/day for 4 weeks, subsequently increased to 600 mg/day, or placebo, and were followed for 16 weeks. Clinical and laboratory assessments were performed at 0, 4, and 16 weeks, and patients were submitted to a cardiopulmonary exercise test at the start and at the end of the study follow up. Results A total of 41 patients were included, 22 in the allopurinol group and 19 in the placebo group. There was a predominance of male participants in the allopurinol group (86.4% vs. 47.4% in the placebo group, p = 0.007). There were no differences in other demographic data or clinical aspects between the two groups. No significant difference was observed between the two groups in the final total exercise time (591.1 seconds in the allopurinol group vs. 596.8 seconds in the placebo group; p = 0.990), nor in the metabolic parameters of the cardiopulmonary test. The allopurinol group showed a better final ischemic threshold, (531.1 seconds vs. 369.9 seconds; p = 0.027). In the clinical evaluation, there was a trend towards improvement in CCS functional classification (81.8% vs. 55.6%; p = 0.071) and a reduction in nitrate consumption (87.5% vs. 53.8%; p = 0,044) in the allopurinol group. Adverse events were rare, equally distributed between groups, of low severity, and did not require protocol interruption. Conclusion Allopurinol did not demonstrate an impact on improving exercise duration in cardiopulmonary exercise testing in patients with refractory angina. However, it was associated with a higher ischemic threshold, a reduction on use of short-acting nitrates and a trend towards improvement in angina functional CCS classification compared to placebo.Table 1 - Cardiopulmonary exercise test Table 2 - Clinical Data
Azevedo et al. (2025) studied this question. Allopurinol raised ischemic threshold by 44% (531.1s vs 369.9s; p=0.027) and reduced nitrate use (87.5% vs 53.8%; p=0.044) but did not improve exercise time in refractory angina.