Circulation, Vol 81, 1260-1270, Copyright © 1990 by American Heart Association
PL Cole, AD Beamer, N McGowan, CO Cantillon, K Benfell, RA Kelly, LH Hartley, TW Smith and EM Antman
Despite large gains in the medical and surgical treatment of angina
pectoris in the past two decades, many patients are refractory to
conventional medical therapy and are unsuitable for a first or, more
commonly, repeat coronary revascularization procedure. We evaluated the
efficacy of perhexiline maleate, a drug with an antianginal mechanism of
action in humans that is as yet unknown, by using a randomized double-blind
placebo-controlled crossover design in 17 patients with refractory angina
who continued to receive maximal antianginal therapy, typically including
nitrates, a beta-blocker, and a calcium channel antagonist. In view of
perhexiline's potential for hepatic and neurological toxicity, plasma drug
levels were monitored and maintained in the 150-600 ng/ml range.
Sixty-three percent of patients were judged perhexiline responders by
objective exercise testing criteria, as compared with 18% of patients on
placebo (p less than 0.05). By blinded review of subjective measures of
anginal frequency and severity, 65% of patients noted an improvement while
on perhexiline, whereas no patient identified the placebo phase with
improvement. Side effects observed in 29% of patients were minor and
related to transient elevations of blood levels of more than 600 ng/ml; no
patient suffered hemodynamic or cardiac conduction abnormalities
attributable to perhexiline. With attention to the pharmacokinetics of
perhexiline's elimination in individual patients, this novel antianginal
agent seems to be safe and effective and deserves further evaluation in
patients already receiving maximal antianginal therapy who are not
candidates for revascularization procedures.
ARTICLES
Efficacy and safety of perhexiline maleate in refractory angina. A double-blind placebo-controlled clinical trial of a novel antianginal agent
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
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