Reviewer: Dr Bengisu KESKİN MERİÇ

Name of the Study: Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease

Published Congress: ESC 2022

Background: Allopurinol, a xanthine oxidase inhibitor used in the treatment of gout, is known to reduce oxidative stress as well as serum uric acid levels. Various mechanisms have been proposed for how allopurinol might improve cardiovascular outcomes. Allopurinol reduces superoxide anions and other free radicals, thus preventing cardiac hypertrophy and atherosclerotic plaque rupture and increasing tissue oxygenation. The importance of serum uric acid level in cardiovascular diseases is controversial. Also, there is no indication for use of allopurinol in asymptomatic hyperuricemia or cardiovascular diseases.

Objective: The aim of this study was to determine whether allopurinol improves cardiovascular outcomes in individuals with ischemic heart disease but who had not been diagnosed with gout.

Methods: Prospective, randomised, open-label, blinded endpoint, multicenter study; 5215 patients over 60 years of age with ischemic disease were included. These patients were randomized to allopurinol and usual treatment. Patients with a diagnosis of gout, advanced renal failure, advanced symptomatic heart failure (NYHA III-IV), and significant liver disease were not included in the study. Non-fatal myocardial infarction (MI), non-fatal stroke, or cardiovascular death were accepted as the primary outcome. Non-fatal MI, non-fatal stroke, cardiovascular death, all-cause death, hospitalization or coronary revascularization due to acute coronary syndrome (ACS), hospitalization for heart failure, all CV hospitalizations and quality of life were considered as secondary outcomes. Cost effectiveness was also evaluated.

Results: The mean follow-up period of the study, which started in February 2014 and ended in September 2021, was 4.8 years, with a mean age of 72 years. 258 (9%) of the allopurinol group and 76 (2.6%) of the usual treatment group withdrew from all follow-up, while 57.4% of the allopurinol group withdrew from randomised treatment during the study. A total of 639 primary outcomes were achieved, 314 (11.0%) in the allopurinol arm and 325 (11.3%) in the usual treatment arm [hazard ratio (HR) 1.04, 95% confidence interval (CI) 0.89–1.21; P = 0.65]. There was no significant difference between the two groups in terms of primary outcomes in different subgroups. In the safety analysis, no difference was observed between the two groups in terms of cancer incidence or all-cause death.

Conclusion: Allopurinol therapy did not improve CV outcomes when added to usual therapy in individuals over 60 years of age with cardiovascular disease.

Interpretations: Allopurinol, which has an antioxidant effect and has been shown to reduce cardiovascular outcomes in various studies; It has not been shown to have a positive effect on cardiovascular outcomes in individuals with ischemic heart disease.