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In 15 patients with angiographically proven coronary heart disease and reproducible exercise induced ischemic ST-segment depression the antianginal effect of Perhexilinmaleat was tested in a cross-over randomized double-blind trial. The patients were treated 4 weeks with a placebo, 2 weeks with 200 mg and 2 weeks with 400 mg/day Perhexilinmaleat. The exercise-induced ischemic ST-segment depression was significantly reduced (p less than 0.001) by Perhexilinmaleat. This calcium-antagonist drug also prolonged the PQ-interval and reduced the heart rate during exercise. Some liver specific enzymes were slightly elevated. These and other side effects more often occurred at the higher dose of 400 mg/day.

The antianginal effect of perhexiline was evaluated in a placebo-controlled double-blind study of 20 patients with stable angina pectoris. Only patients with documented myocardial infarction of more than 6 months' standing and with ST-segment depression on exercise were admitted to the study. Objective parameters of bicycle stress tests at a submaximum level of 50 watts and a maximum exercise level were evaluated. Subjective data such as nitroglycerin consumption and incidence of anginal attacks per week were obtained from the patients' self-maintained records. No negative chronotropic effect of perhexiline was found at rest. At a submaximum exercise level with unchanged double-product, a significantly lower heart rate (p less than 0.05) and a significant reduction in ST-segment depression were observed in comparison with the placebo. At maximum exercise level an increase in exercise tolerance of 8.1% and in aerobic capacity of 8.3% resulted in a significant increase in the double-product (p less than 0.01), with a shift in the blood pressure/heart rate ratio. Discontinuation of exercise occurred at the same heart rate, but at a markedly higher level of exercise attainment. Heart rate on exercise proved to be the most valuable parameter in this study for the evaluation of the aerobic capacity of the individual patient. Nitroglycerin consumption and frequency of anginal attacks per week were reduced, but were not of statistical significance. Side-effects occurred in 6 patients, but these did not require termination or reduction of medication. The selective effect on heart rate during exercise opens a new field of application for perhexiline in comparison with beta-blocking agents.