Sustained effect of orally administered isosorbide dinitrate on exercise performance of patients with angina pectoris

The efficacy of oral isosorbide dinitrate was evaluated in nine hospitalized patients with chronic angina pectoris and positive maximal bicycle exercise tests. Patients were randomized double-blind to receive either 20 mg of isosorbide dinitrate or placebo on successive days after a control maximal upright bicycle exercise test. On each day hourly exercise tests were performed for 4 hours after drug administration to an end point of fatigue or angina pectoris. Mean systolic blood pressure 4 hours after the administration of isosorbide dinitrate was 25 mm Hg less than the control value (P less than 0.001). The values for resting heart rate and exercise-attained heart rate-blood pressure product were not significantly different from the values after placebo. The duration of exercise was prolonged (P less than 0.025) for at least 3 hours, and less ST depression (P less than 0.01) was observed up to 3 hours after the administration of isosorbide dinitrate compared with control values. The demonstration of sustained imporved exercise performance and previously described hemodynamic effects with the use of higher doses suggests that adequate blood levels of isosorbide dinitrate or mononitrate metabolites may be important for the efficacy of oral organic nitrates.