Effect of nipradilol on silent myocardial ischemia and heart rate variability in chronic stable angina

Purpose: Silent myocardial ischemic episodes as well as decreased heart rate variability (HRV) indices are associated with an unfavorable outcome in patients with coronary artery disease. Nipradilol, which is a non-selective beta-adrenergic and nitrate-like vasodilator anti-anginal agent developed in Japan, may ameliorate silent myocardial ischemia, while it also improves exercise tolerance and HRV indices in patients with chronic stable angina. Methods: To investigate the effect of nipradilol (6 mg daily) on silent myocardial ischemic episodes and HRV indices, and to study its effect on the relationship between them, 24 patients with chronic stable angina underwent exercise treadmill testing and a 24-hour ambulatory electrocardiogram (ECG). The study protocol utilized a single blind, 4-week placebo-controlled design. The HRV indices from ambulatory ECG included mean RR (ms), SDNN (ms), SDANN (ms), SD (ms), rMSSD (ms), pNN50 (%); frequency analysis of HRV consisted of total (ms, 0.01-1.00 Hz), low (ms, 0.04-0.15 Hz) and high (ms, 0.15-0.40 Hz) components. Results: Nipradilol significantly decreased the mean heart rate at submaximal and maximal exercise and the mean pressure rate product at submaximal and maximal exercise. It significantly improved exercise-induced maximal ST segment depression from -1.7 +/- 0.6 mm to -1.1 +/- 0.7 mm (p < 0.05). Silent myocardial ischemic episodes recorded during the 24-hour ambulatory ECG significantly decreased after nipradilol administration. Nipradilol also significantly influenced several HRV indices as well as the relationship between silent myocardial ischemic episodes and the HRV indices. Nipradilol significantly increased SD, rMSSD, pNN50, total spectra, low frequency spectra and high frequency spectra. In addition, nipradilol significantly decreased the LF/HF ratio from 1.7 (1.5-2.0) to 1.5 (1.3-1.8). These effects of nipradilol on HRV indices concomitantly occurred with the reduction in silent myocardial ischemic episodes. Conclusion: Nipradilol was found to effectively improve the episodes of silent myocardial ischemia as well as exercise-induced ischemia probably due to its beta-blocking properties and not nitrate-like actions. In addition, nipradilol also had a favorable effect on the HRV indices.