[Anti-angina effectiveness of isosorbide dinitrate in an acute trial and following continuous 4-week therapy with 40 mg 6 times a day].

Ten patients with angiographically proven coronary heart disease, stable exercise-induced angina pectoris, and reproducible ST-segment depression were treated with isosorbide dinitrate (ISDN) tablets in daily doses of 240 mg (6 X 40 mg) and placebo (PL) for 28 days each on the basis of a randomized double-blind protocol with intraindividual cross-over. ISDN treatment resulted in a sustained reduction of anginal attacks with a weekly mean rate ranging from 1.4 (3rd week) to 3.9 (4th week) as compared to 10.2 (2nd week) to 11.7 (4th week) during placebo treatment (P less than 0.001). Ischemic response during stress testing (sum of ST-segment depressions) was significantly improved during ISDN treatment as compared to placebo. Day 1: 56% (P less than 0.01); day 7: 30% (P less than 0.01); day 28: 49% (P less than 0.001). Heart rate and arterial blood pressure in the upright position were different between ISDN and placebo on day 1 and day 7 of the treatment phases (P less than 0.02), but not on day 28. Nitrate responsiveness with regard to blood pressure and heart rate was restored after a drug-free interval of 2 days. The plasma concentrations for ISDN and the mononitrate metabolites exhibited a constant ratio during the treatment period. Thus, therapy with 6 X 40 mg ISDN per day resulted in a sustained reduction of anginal attacks and preserved improvement of ischemic ST-segment depression during exercise in upright position.