BARCELONA — Allopurinol treatment for 6 weeks significantly improved symptoms of chronic, stable angina in a randomized, placebo-controlled, crossover study of 60 patients.
Allopurinol administered at labeled dosages produced three significant improvements during an exercise treadmill test, which were the study's primary end points: increased total exercise time, increased time to ST segment depression, and increased time to angina, Dr. Awsan Noman said at the annual congress of the European Society of Cardiology.
Although the means by which allo-purinol produced these effects are not known, one hypothesized mechanism is sparing oxygen and cutting superoxide production by blocking xanthine oxidase. Allopurinol might also improve peripheral endothelial function, said Dr. Noman, a cardiologist at the Royal Infirmary in Edinburgh. The testing began because studies in animals had shown that it cuts oxygen demand in the heart without changing cardiac output.
The study enrolled patients with chronic stable angina and coronary artery disease. It excluded patients with recent myocardial infarctions or revascularization, patients with impaired left ventricular function, and those with impaired renal function. The researchers initially screened 101 patients and enrolled 65 to get the 60 who finished the study.
Patients were randomized to receive allopurinol at 100 mg orally once daily for 1 week, followed by 300 mg once daily for 1 week, and then 300 mg b.i.d. for 4 weeks, or 6 weeks on placebo. After 6 weeks all patients crossed to the opposite regimen, Dr. Noman said.
Average patient age was 64 years and 80% were men; 70% of patients had Canadian Cardiovascular Society class II angina, 15% had class I, and 15% had class III. All patients were on aspirin, 97% were on a statin, 87% were on a beta-blocker, and many patients also received other medications.
After each 6-week regimen, patients underwent exercise treadmill testing. The allopurinol patients had significant increases in their total exercise time, time to ST depression, and time to angina compared with the placebo group and compared with baseline. (See box.)
These benefits were achieved without any changes in resting heart rate, blood pressure, or rate-pressure product. When patients were on allopurinol, their maximum heart rate was 5% higher and the maximum rate-pressure product was 8% higher. These findings “argue against allo-purinol acting like a beta-blocker or other rate-limiting agents,” Dr. Noman said.
Allopurinol also had the expected effect of lowering serum levels of uric acid, cutting the values by an average of more than half. Patients face no known risk from low blood levels of uric acid, he said.
Further research needs to better define how allopurinol helps angina patients, and to identify an optimal regimen, Dr. Noman said.
Dr. Noman did not disclose any conflicts of interest.
Benefits were achieved without any changes in resting heart rate, blood pressure, or rate-pressure product.
Source DR. NOMANfpnews@elsevier.com
Source ELSEVIER GLOBAL MEDICAL NEWS