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Allopurinol May Act as Anti-Ischemic in Angina


 

Major Finding: Allopurinol in patients with angina pectoris improved time to ST depression from 232 seconds at baseline to 249 seconds and 298 seconds in the placebo and treatment groups, respectively, for an absolute improvement of 43 seconds (19%).

Data Source: A randomized, placebo-controlled, double-blinded, crossover study of 65 patients.

Disclosures: The study was funded by the British Heart Foundation. The University of Dundee and one of the study authors have applied for a patent for the use of xanthine oxidase inhibitors to treat anginal chest pain. Dr. Noman and the other authors declared no conflicts of interest. Dr. Antony and Dr. Dargie indicated that they have no financial conflicts.

High-dose allopurinol, a safe and inexpensive xanthine oxidase inhibitor used for decades for the treatment of gout, also appears to be an effective anti-ischemic drug in patients with angina pectoris, according to findings from a randomized, placebo-controlled study.

In 65 patients in the double-blind crossover study, allopurinol was shown during a standard exercise test to significantly improve median overall time to ST depression—the primary end point of the study—by a point estimate (the absolute difference between allopurinol and placebo) of 43 seconds, for a 19% improvement. It also significantly improved median exercise time and time to chest pain by point estimates of 58 and 38 seconds, respectively, Dr. Awsan Noman of the University of Dundee, Scotland, and colleagues reported online June 8 in The Lancet.

Time to ST depression improved from 232 seconds at baseline to 249 seconds and 298 seconds in the placebo and treatment groups, respectively; total exercise time improved from 301 seconds at baseline to 307 seconds and 393 seconds in the two groups, respectively; and time to symptoms improved from 234 seconds at baseline to 272 seconds and 304 seconds in the two groups, respectively, the investigators reported (Lancet 2010 June 8 [doi:10.1016/S0140-6736(10)60391-1]).

The patients were aged 18-85 years and had angiographically documented coronary artery disease, a positive exercise tolerance test, and stable chronic angina pectoris for at least 2 months prior to enrollment. They were randomized to receive allopurinol daily or placebo for 6 weeks. Allopurinol in the first phase of the study was given at a dose of 100 mg once daily in the first week, 300 mg once daily in the second week, and 300 mg twice daily in weeks 3-6; the 600-mg daily dose was used in the crossover phase, which immediately followed the first phase, because it was shown to be the most effective dose for improving endothelial function and oxidative stress, they said.

The findings suggest that “endogenous xanthine oxidase activity contributes somehow to exercise-induced myocardial ischaemia,” the investigators wrote, adding that the magnitude of the anti-ischemic effect of allopurinol in this study appeared similar to that seen with other antianginal drugs.

“Allopurinol might now be regarded as a potential drug for angina,” the investigators wrote, citing numerous advantages over other available antianginal drugs, including lower cost, a favorable long-term safety record over more than 40 years of use in gout patients, and better tolerability; allopurinol does not reduce blood pressure or heart rate, and does not cause side effects such as headache and tiredness common with nitrates and beta-blockers, they noted.

Further study is needed to better characterize the “the precise place of allopurinol in the management of angina pectoris,” but it may be a particularly appealing drug for use in developing countries where the availability of more expensive treatments is limited, they concluded.

Stable angina is the most frequent initial presentation of coronary heart disease; the condition can lead to acute coronary syndrome, particularly in higher risk groups; and it also has high rates of residual symptoms and impaired quality of life even in well-managed patients.

Nonetheless, the condition has received little attention, compared with unstable angina and other acute coronary syndromes, Dr. Renjith Antony and Dr. Henry J. Dargie of the Scottish Advanced Heart Failure Service, Golden Jubilee National Hospital, West Dunbartonshire, Scotland, said in an editorial.

The report by Dr. Noman and colleagues is interesting and welcome in that it will “focus attention on the unmet needs of patients with the most common, and frequently troublesome, manifestation of coronary heart disease,” they wrote (Lancet 2010 June 8 [doi:10.1016/S0140-6736(10)60578-8]).

Allopurinol significantly improved median overall time to ST depression, the study's primary end point.

Source DR. NOMAN

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