SLOW RELEASE ISOSORBIDE-5-MONONITRATE THERAPY IN ANGINA-PECTORIS - EFFECTS OF EXERCISE PERFORMANCE AND HEMODYNAMICS

The possibility of maintaining preload reduction and enhancement of exercise tolerance during an interval treatment with 100 mg/day of slow-release isosorbide-5-mononitrate (IS-5-MN) was investigated in 12 patients (aged 57 +/- 5.0 years) with angiographically confirmed coronary artery disease and chronic stable angina pectoris. The effects of a single dose (acute test) were compared with those following an 8-day (chronic) regimen of mononitrate administration. Two hours after administration of 100 mg sustained-release IS-5MN, mean resting pulmonary artery pressure (PAP), measured with a Swan-Ganz catheter, was reduced by 32% (p < 0.001) and at submaximal exercise level (50 W, 3 min) by 37% (p < 0.001). At individually highest comparable work loads mean PAP was reduced by 37% (p < 0.001), and at maximal work load the PAP reduction was 14% (p < 0.05). At the end of 1 week of therapy with sustained-release IS-5-MN a slight, clinically irrelevant reduction of hemodynamic effects was recorded. Work capacity increased after 1 h by 79% (264 +/- 154 vs. 472 +/- 180 W X min, p < 0.01), still significantly above base-line 10 h after nitrate administration. No difference from baseline was demonstrable 24 h after medication. During interval therapy the improved work capacity was fully maintained (chronic, 1 h: 280 +/- 119 vs. 532 +/- 160 W X min, p < 0.001). There was no significant difference between the plasma IS-5-MN levels at acute and chronic therapy. During interval therapy with sustained-release IS-5-MN, hemodynamics and exercise tolerance were durably improved. Thus, the once-daily intake is beneficial for patient compliance and prevents tolerance development during long-term therapy of coronary artery disease.