The effectiveness of allopurinol in improving ischemic symptoms or exercise tolerance in patients with chronic coronary syndromes: a systematic review and meta-analysis of randomized clinical trials

Abstract Background Angina pectoris, a prevalent symptom of coronary artery disease (CAD), significantly reduces patient’s quality of life and exercise capacity. Allopurinol, a xanthine oxidase inhibitor, has been suggested as a potential therapeutic agent for improving myocardial ischemia and endothelial function, thereby benefiting individuals experiencing myocardial ischemic symptoms. Although some evidence indicates that allopurinol may enhance angina symptoms and exercise capacity, findings remain inconsistent, and no comprehensive synthesis of randomized clinical trials (RCTs) has been conducted to date. Purpose This study aimed to evaluate the efficacy of allopurinol in alleviating angina pectoris and improving exercise tolerance in patients with CAD. Methods A systematic review and meta-analysis of RCTs were conducted in accordance with Cochrane guidelines. A literature search was performed using EMBASE and PUBMED to identify RCTs that assessed the effects of allopurinol in patients with CAD or angina pectoris compared to a control group. The primary outcomes were improvements in angina symptoms and exercise tolerance. Results A total of 83 articles were screened, of which five were included in the study. However, only four RCTs provided comparable data for quantitative analysis and only three were placebo controlled. Meta-analysis of these three RCTs, comprising 121 patients, demonstrated that allopurinol had a neutral effect on the change in total exercise duration (mean difference MD 17.44, 95% confidence interval CI -43.63 to 78.51, P = 0.58) with significant heterogeneity (I² = 71%). Regarding the change in time to angina onset, only two RCTs involving 101 patients provided comparable data, indicating a trend favoring allopurinol (MD 36.7, 95% CI -10.13 to 83.53, P = 0.12, I² = 0%); however, the results did not reach statistical significance. Conclusion This meta-analysis indicates that, to date, there is no robust evidence supporting the benefit of allopurinol in improving exercise tolerance or delaying the onset of angina pectoris during exertion. However, the available studies on this topic are limited in size and exhibit substantial heterogeneity, suggesting that the current evidence is insufficient to definitively determine the effectiveness of allopurinol for myocardial ischemic symptoms. Robust RCTs are needed to address this question and provide definitive evidence regarding this theme.Change in Total Exercise duration Change in Time for Angina Onset