Exercise capacity after single and twice-daily doses of nicorandil in chronic stable angina pectoris

In a double-blind parallel group study, 46 patients with chronic stable angina were randomized, after a 2-week placebo washout period, to 1 of 3 treatment groups for an additional 2 weeks. Groups 1 and 2 received nicorandil (5 mg, N = 5; 10 mg, N = 10) twice daily, respectively, increasing to 10 and 20 mg (n = 20) twice daily after 1 week of treatment; group 3 continued to receive placebo. A symptom-limited Bruce protocol exercise test was performed before and 2 hours after the initial dose and, after 2 weeks of treatment, 2 and 12 hours after administration. The following parameters were measured: resting, peak exercise and recovery blood pressure and heart rate, exercise duration, time to onset of angina and time to 1 mm of ST-segment depression.

After initial dosing, there were significant increases in exercise duration (16%—n = 5, N = 10 vs −2% [placebo]) and time to onset of angina (20%, N = 5; 26%, N = 10 vs 5% [placebo]) (p < 0.05). Time to onset of 1 mm of ST-segment depression increased in the nicorandil-treated groups compared with that in the placebo group (27%, N = 5; 25%, N = 10 vs 8% [placebo]). Calculated total exercise work increased in both nicorandil groups compared with exercise work in the placebo group (30%, N = 5; 19%, N = 10 vs 3% [placebo]). A decrease in resting systolic blood pressure (12%) in the 10-mg group was the only significant alteration in the hemodynamic parameters. After 2 weeks of treatment there was a significant increase in time to onset of angina both 2 hours (38%, N = 10; 32%, N = 20 vs −2%) and 12 hours (23%—n = 10, N = 20 vs −2% [placebo]) (p < 0.05) after dose administration in both nicorandil groups compared with placebo group. Exercise duration, time to 1 mm of ST-segment depression and total exercise work increased in the nicorandil groups but these did not reach statistical significance. There was no significant change in the hemodynamic parameters at rest, peak exercise or recovery. Thus, nicorandil, 10 or 20 mg, administered twice daily improves exercise capacity both acutely and after chronic administration without significant alteration in blood pressure or heart rate.