Comparison of the Effect of Isosorbide‐5‐Mononitrate and Isosorbide Dinitrate in a Slow‐Release Form on Exercise‐Induced Myocardial Ischemia

A randomized, double blind, placebo-controlled crossover study on 20 patients with exercise-induced angina pectoris and reproducible ST-segment depression during exercise-stress test was performed to compare the effect of a single dose of 120 mg of isosorbide dinitrate in a slow-release form with that of a twice-daily application of 20 mg of isosorbide-5-mononitrate. Symptom-limited exercise tests were done, and nitrate plasma levels were measured in the subjects 6, 10, and 24 hours after the first administration of the drug. Both drugs produced a highly significant reduction in the size of exercise-induced ST-depressions (P less than .001) 6 and 10 hours after the first administration of isosorbide dinitrate as well as 6 hours after the first and 4 hours after the second dose of isosorbide-5-mononitrate. The effect was still significant (P less than .05) 24 hours after the administration of isosorbide dinitrate in a slow-release form and 18 hours after the second dose of isosorbide-5-mononitrate. In the case of the drug isosorbide dinitrate, nitrate plasma levels for its metabolite, isosorbide-5-mononitrate, were highest 10 hours after first application. In the case of the drug isosorbide-5-mononitrate, nitrate plasma levels were highest 4 hours after the second dose. Two 20 mg doses of isosorbide-5-mononitrate and a single dose of 120 mg isosorbide dinitrate in a slow release form have a comparable effect on the reduction of exercise-induced ST-segment depressions.