Equal anti-ischemic properties of isosorbide dinitrate plus verapamil and isosorbide dinitrate plus propranolol. A...

Although nitrates are the basic treatment for patients with ischemic heart disease and numerous clinical studies have compared the anti-ischemic effects of different combinations with beta-blockers and/or calcium antagonists, no study is known on a controlled intraindividual comparison of the combination nitrate plus beta-blocker with the combination nitrate plus a heart rate-decreasing calcium-antagonist. Therefore we performed a randomized, double-blind and crossover study to compare the effects of 80 mg isosorbide dinitrate in slow-release form (ISDN, once-daily) plus 120 mg verapamil (t.i.d.) with those of 80 mg ISDN plus 80 mg propranolol (b.i.d.). After these two phases of 3 weeks' duration respectively, patients received the combination of all three drugs with the same dosages in a single-blind manner. In addition to the standard inclusion criteria, a pathological exercise-ECG even after ISDN was required as well as a left ventricular ejection fraction (EF) of greater than or equal to 35%. This protocol could be completed in 26 of the 30 enrolled patients. The combination ISDN plus verapamil proved to exert the same anti-ischemic effects as the combination ISDN plus propranolol. The triple therapy showed a further improvement of exercise induced ischemia without deterioration of the EF at rest or during exercise. Even though only this triple therapy led to an optimal anti-ischemic result in about one third of the patients, it should be initiated cautiously, since symptomatic bradycardia may occur.