Key Points
- Allopurinol had previously shown an improvement in exercise time and qualitative chest pain assessment in patients with ischemic heart disease.
- ALL-HEART randomized over 5,700 patients without gout to receive allopurinol in addition to usual care versus usual care alone. The dose of the xanthine oxidase inhibitor was up-titrated to a total of 600 mg daily.
- The primary outcome, a composite of nonfatal myocardial infarction, nonfatal stroke or cardiovascular death, was not found to be different between the two groups, suggesting no benefit for the drug, and likely settling the question for good.
The inflammation cascade has long been implicated in the progression of atherosclerosis. As such, various anti-inflammatory medications have been studied for both prevention and treatment of heart disease. Allopurinol, a xanthine oxidase inhibitor used for the treatment of gout, had garnered similar attention after studies showed found the drug to be associated with improvement in exercise time and chest pain in those with gout and ischemic heart disease. ALL-HEART, therefore, attempted to address whether this association held true. In a Hot Line session at the 2022 European Society of Cardiology Congress, today, Dr. Isla MacKenzie (University of Dundee, United Kingdom), presented the results of the largest randomized clinical trial to assess the cardiovascular effects of allopurinol.
For this multi-center, randomized, open-label clinical trial, patients were recruited from over 400 practices across the United Kingdom. Participants were at least 60 years of age with documented ischemic heart disease and no history of gout. Over 5000 patients were analyzed, with a mean follow up of 4.8 years. In the intention to treat analysis, allopurinol, which was prescribed to 2871 patients at a dose of 600 mg daily, failed to demonstrate any effect on the primary outcome, a composite of nonfatal myocardial infarction, nonfatal stroke or cardiovascular death when compared to usual care (11.0 vs. 11.3%, HR 1 .04 (95% confidence interval [CI] 0.89–1.21, p=0.65)). Furthermore, the drug failed to demonstrate a benefit in any of the components of the primary outcomes when assessed separately.
Secondary time to event analyses included hospitalization for acute coronary syndrome, hospitalization for heart failure, hospitalization for coronary revascularization, and all cardiovascular hospitalizations, none of which were improved by the addition of allopurinol to the medical regimen.
Given the widespread use of allopurinol in patients with gout, many of whom have existing ischemic heart disease, Dr. MacKenzie stated that their group was “pleased to finally put this question to rest”. They concluded that allopurinol should not be used in the treatment of ischemic heart disease in patients without gout.