The underlying mechanisms of
myocardial ischemia in
microvascular angina may include endothelial dysfunction, abnormal smooth muscle tone, and abnormal autonomic control of coronary microvasculatures. This randomized, double-blind, placebo-controlled, crossover study was conducted to evaluate the effect of
nicorandil (a
nitrate-
potassium channel opener)
therapy on exercise-induced
myocardial ischemia and cardiac autonomic activity in 13 patients with
microvascular angina. After a 2-week placebo run-in period, patients were randomly assigned to the first 2-week treatment with
nicorandil 5 mg tid or placebo, then crossed over to the second 2-week treatment after a 2-week washout period. Treadmill exercise tests and 24-hour ambulatory electrocardiogram monitoring were performed at the end of each treatment phase. The results showed that both time to 1-mm ST depression and total exercise duration were significantly prolonged with
nicorandil treatment compared with placebo (p = 0.026 and 0.036, respectively). Maximum exercise ST depression also tended to be less with
nicorandil treatment than with placebo (p = 0.083). Compared with 10 healthy control subjects, study patients had significantly reduced heart rate variability in both low- and high-frequency bands while receiving placebo.
Nicorandil treatment did not change the altered heart rate variability in either time domain or spectral analysis. Systemic hemodynamics were also unchanged with
nicorandil treatment. Thus, 2-week oral
nicorandil therapy moderately improved exercise-induced
myocardial ischemia without modifying the already altered cardiac autonomic activity, suggesting that
nicorandil might have a direct vasodilatory effect on coronary microvasculatures in patients with
microvascular angina.