Allopurinol fails to improve outcomes in ischemic heart disease
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In patients with ischemic heart disease older than 60 years, the uric acid-lowering drug allopurinol did not improve CV outcomes, according to results of the ALL-HEART trial presented at the European Society of Cardiology Congress.
Isla Mackenzie, MBChB (Hon), PhD, FRCP Edin, FBPharmacolS, professor of cardiovascular medicine and honorary consultant physician at University of Dundee and Ninewells Hospital, Dundee, U.K., and colleagues conducted the ALL-HEART trial to determine whether allopurinol, a xanthine oxidase inhibitor used to treat gout, could improve major CV outcomes in patients with ischemic heart disease compared with usual care.
“We usually use [allopurinol] to treat gout and prevent gout flares because it lowers the uric acid levels and prevents patients from having really painful attacks of gout,” Mackenzie said at a press conference. “It is not usually used in heart disease.”
Allopurinol was selected for study because of its antioxidant and uric acid-lowering effects, she said.
The randomized, open-label trial included 5,721 patients older than 60 years with ischemic heart disease but no history of gout recruited from 424 primary care practices in the U.K. The primary outcome was CV death, nonfatal MI or nonfatal stroke. Mean follow-up was 4.8 years. Patients were assigned allopurinol 600 mg daily or usual care.
The primary outcome did not differ between the groups (HR = 1.04; 95% CI, 0.89-1.21; P = .65), Mackenzie said.
There were also no differences between the groups in CV death (HR = 1.1; 95% CI, 0.85-1.43; P = .48), nonfatal MI (HR = 0.97; 95% CI, 0.78-1.21; P = .81), nonfatal stroke (HR = 1.2; 95% CI, 0.89-1.6; P = .23) and all-cause death (HR = 1.02; 95% CI, 0.87-1.2; P = .77), according to the researchers.
“This was a definitively neutral trial all around,” Mackenzie said at the press conference. “ALL-HEART ... provides robust evidence of the effect of allopurinol in these patients, a question that has been unanswered for many years. Allopurinol remains an important medication when we are managing patients with gout, but I believe that other avenues for treatment of ischemic heart disease need to be explored in the future.”
She said the results should not have much of an effect on the inflammation hypothesis of CVD.
“I don’t think allopurinol is the most anti-inflammatory drug around,” Mackenzie said at the press conference. “Other drugs with anti-inflammatory actions have shown benefit, like colchicine, which has a different mechanism of action, but which is also used in gout. I’m not sure that this [trial] adds hugely to the anti-inflammatory knowledge, because allopurinol has a number of mechanisms of action.”
Perspective
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Allopurinol, an important medication for gout, has also been thought to have other possible effects for treatment of ischemic heart disease, and is something we thought might be good for preventing secondary events in patients with ischemic heart disease. ALL-HEART, a well-conducted study with a sizable number of patients, showed that after 7 years, there was no improvement in outcomes in patients with ischemic heart disease treated with allopurinol compared with standard care. The agent did not reduce MIs, strokes or CV deaths.
The study answers an important question that while allopurinol is an important medication for gout, it doesn’t appear to be effective for treatment of ischemic heart disease and prevention of secondary events in those patients. We don’t know exactly why it did not work, but it does not appear that the specific pathway of xanthine oxidase inhibition is helpful to reduce the progression of ischemic heart disease or acute events in those patients. We need to look at other possibilities for treatment of ischemic heart disease.
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Mackenzie I, et al. Hot Line 3. Presented at: European Society of Cardiology Congress; Aug. 26-29, 2022; Barcelona, Spain (hybrid meeting).
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