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CARDIOVASCULAR DISORDERS Omar
Badawi, Section Advisor
High-dose allopurinol for chronic stable angina pectoris
Key point: In study recently published in
Lancet, high-dose allopurinol (600 mg/d) increased exercise
capacity and decreased effort-related symptoms in patients with chronic
stable angina pectoris.
Finer points: Sixty-five patients 18 to 85 years of
age with angiographically documented coronary artery disease, a positive
exercise tolerance test, and a history of symptoms of chronic, stable,
effort-induced angina pectoris for at least 2 months participated in
this 12-week, double-blind, placebo-controlled, crossover study. Using
computer-generated randomization, patients were assigned to either
allopurinol or placebo for 6 weeks. Allopurinol was dosed as 100 mg once
daily for the first week, 300 mg once daily for the second week, and 300
mg twice daily for the duration of the treatment period. Patients were
then crossed over, without any washout period, to the other treatment
for an additional 6 weeks. During the study, patients were permitted to
continue all concomitant antianginal medications. The primary endpoint
in the study was the amount of time to ST depression, and the secondary
endpoints were total exercise time and time to chest pain.
In the first treatment period, 60 of 65 patients were included in
final analysis; 28 were randomized to allopurinol and 32 were randomized
to placebo. Three patients randomized to allopurinol and two patients
randomized to placebo withdrew during the first treatment period for
reasons unrelated to the study. In the second treatment period, all 60
patients were included in the final analysis; 32 were randomized to
allopurinol and 28 were randomized to placebo.
For the primary endpoint, high-dose allopurinol significantly
increased the median time to ST depression to 298 s from a baseline of
232 s (vs. 249 s for placebo, P = 0.0002), yielding an absolute
difference between groups of 43 s (95% CI 31–58). For the
secondary endpoints, high-dose allopurinol significantly increased
median total exercise time to 393 s from a baseline of 301 s (vs. 307 s
for placebo, P = 0.0003), yielding an absolute difference
between groups of 58 s (95% CI 45–77); and high-dose allopurinol
increased the time to chest pain from a baseline of 234 s to 304 s (vs.
272 s for placebo, P = 0.001), yielding an absolute difference
between groups of 38 s (95% CI 17–55). No treatment-related
adverse effects were reported in the study.
What you need to know: According to the
investigators, the exact mechanism of the antiangina effects of
allopurinol are unknown. The investigators speculated that allopurinol
may exert its effects by inhibiting the enzyme xanthine oxidase, an
enzyme that increases oxygen wastage in the myocardium by improving
coronary blood flow, and/or by decreasing left ventricular
afterload.
An accompanying comment in the same issue of Lancet noted
that additional studies are “needed to confirm
allopuri-nol’s putative anti-ischemic effects and to better
understand its mechanisms of action” but that the results are
promising and may yield new treatment options for patients suffering
from angina pectoris.
What your patients need to know: Allopurinol has a
favorable safety record, has been used as a treatment for gout for more
than 40 years, and is considerably less expensive than other antianginal
drugs. While preliminary data suggests that high-dose allopurinol may be
an alternative treatment for chronic stable angina pectoris, more data
are needed to confirm the findings.
Sources:
Related resources on www.pharmacist.com
Posted by Alex Egervary (agervary@aphanet.org)
July 26, 2010, 4:15 pm
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