Effects of nicorandil on rest and effort angina unresponsive to combination therapy with a calcium antagonist and oral nitrate.

The efficacy of nicorandil, a new anti-anginal agent, was evaluated in 11 patients with rest and effort angina not inhibited by combination therapy with a calcium antagonist and an oral nitrate. Electrocardiographic findings during an attack demonstrated ST depression in seven patients, ST elevation in three, and either elevation or depression in two. Coronary angiography in nine patients revealed significant stenosis (greater than or equal to 75%) in eight. Angina persisted in all 11 patients in spite of treatment with 120 to 360 mg/day of diltiazem or 80 mg/day of nifedipine plus 20 to 160 mg/day of isosorbide dinitrate. Three patients were receiving beta-blocker as well; seven were receiving antiplatelet therapy. During combination therapy, patients had between 3.7 and 25 anginal attacks per week (mean +/- SD, 12.2 +/- 6.9). When nicorandil in a dosage of 20 to 40 mg/day was added to the regimen, the mean number of attacks dropped significantly (P less than 0.01) to 1.4 +/- 1.8 times/week. Two patients did not respond to nicorandil. When placebo was substituted for nicorandil in eight of nine responders, the frequency of attacks increased significantly (P less than 0.05) from 0.6 +/- 0.7 to 6.7 +/- 4.8 times/week. Nicorandil did not affect heart rate or blood pressure. These results suggest that nicorandil inhibits rest and effort angina unresponsive to usual doses of calcium antagonist and oral nitrate.