Acute effect of various doses of isosorbide-5-mononitrate on hemodynamic and exercise performance in coronary artery disease.

The optimal dose of nitrates is still controversial, as chronic usage of too high a dose may result in a decrease in vascular response. The dose should be determined to reduce preload acutely, and not to decrease the activity during chronic therapy. To determine this dose, 50 patients with angiographically confirmed coronary artery disease were studied. The effects on heart rate and mean systemic and pulmonary arterial pressures at rest and during exercise, and work capacity and duration were measured. The patients were classified into 5 groups, receiving placebo or isosorbide-5-mononitrate, 5, 10, 20 and 50 mg, respectively, as a single oral dose. Placebo had no effect on the measured parameters. All doses of isosorbide-5-mononitrate reduced mean pulmonary arterial pressure: 10 mg--by 16% at rest and 24% during exercise; 20 mg--24% and 34%, respectively (a near maximal effect); and 50 mg--27% and 38%. Similar results were found also for work capacity: 10 mg increased work capacity by 33%; 20 mg--79%; and 50 mg--56%. Thus, the therapeutically optimal single dose is about 20 mg. Higher doses produce no additional benefit and increase the risk for tolerance development.