Comparative efficacy of high-dose versus low-dose nicorandil therapy for chronic stable angina pectoris

Nicorandil therapy was compared with placebo therapy in 11 patients with chronic stable angina pectoris. A computer-assisted treadmill exercise test was performed after administration of either 10 or 30 mg of nicorandil. Analysis of variance showed a significant difference among placebo and nicorandil treatments (p less than 0.01). Ten milligrams of nicorandil prolonged time to onset of ischemia 36% (p less than 0.05) but increased the exercise duration only 15%. Thirty milligrams of nicorandil prolonged time to onset of ischemia 82% (p less than 0.01) and exercise duration 45% (p less than 0.01). Both time to onset of ischemia and exercise duration increased progressively from the 10-mg to the 30-mg dose (p less than 0.05). Heart rate at rest was significantly higher and systolic pressure at rest significantly lower with 30 mg of nicorandil than with placebo. After administration of 30 mg of nicorandil there was a significant reduction in ST depression associated with a slight decrease in the double product at the end of Bruce stage 2 exercise. The peak double product was greater after administration of 30 mg of nicorandil than after placebo, indicating an increased myocardial oxygen supply to the ischemic area. The plasma concentration of nicorandil averaged 78 +/- 83 ng/ml with the 10 mg and 313 +/- 142 ng/ml with 30 mg. There was an increase in exercise duration of more than 1 minute in 8 of 9 patients who had plasma nicorandil concentrations greater than 100 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)