A controlled single-dose study of the efficacy, dose response and duration of action of nicorandil in angina pectoris.

Nicorandil is a vasodilator that acts on the venous and arterial beds of the systemic circulation. It reduces both cardiac preload and afterload, as well as improving coronary blood flow. The present study assessed the efficacy, tolerability, duration of action and optimal single dose of nicorandil in patients with stable angina pectoris. Treadmill exercise tests were undertaken by 8 patients at 2 and 6 hours after single oral doses of 20, 40, and 60 mg of nicorandil, and placebo. Doses were administered at weekly intervals in this double-blind, cross-over study. The duration of exercise to onset of angina was increased by 58, 96 and 125 seconds over baseline values (p less than 0.01) with the 20-, 40- and 60-mg doses of nicorandil, respectively. Significant improvement in exercise capacity compared with the effects of placebo was maintained at 6 hours after administration. The antianginal activity was accompanied by a marked reduction in blood pressure both at rest and during exercise, which resulted in severe dizziness and fainting in 2 of 6 patients after the 60-mg dose. However, significant reflex tachycardia occurred only at 2 hours after the 60-mg dose. Plasma concentrations of nicorandil correlated with percent reductions in blood pressure at 2 hours after administration (p less than 0.001) and with increasing total exercise work load (p less than 0.01). The incidence of adverse events appeared to be dose related. Headache and dizziness accounted for most of the reported events. The 20-mg single dose of nicorandil was considered to provide the best combination of antianginal activity and tolerability in this study.

RCT Entities:   Population Interventions Outcomes