LONG-TERM TREATMENT WITH MOLSIDOMINE SR IN PATIENTS WITH CORONARY-ARTERY DISEASE

In 20 patients with angiographically confirmed coronary artery disease the long-term efficacy of 8 mg molsidomine twice a day was studied in comparison to placebo over three weeks. Exercise tests were performed at day 1, day 11 and day 21 at times before, 2 hours, 4 hours and 8 hours after medication of molsidomine sr or placebo in a double-blinded manner. Ischemic ST-segment depression was measured during exercise and rest as well as blood pressure, heart rate and plasma levels of molsidomine and SIN-1. Maximal reduction of ST-segment depression of 54% and 42% occurred 2 hours after medication at day 1 and day 11, and of 37% at 4 hours after medication at day 21. Significant duration of action lasted at least 4 hours, after 8 hours a still remarkable but no more significant reduction of ST-segment depression of up to 33% was found. After three weeks of treatment with 8 mg molsidomine sr twice a day a persistant and significant reduction of ST-depression was found. Systolic blood pressure did not change significantly, diastolic blood pressure remained significantly depressed after day 1 and day 21. No changes of heart rate were seen. Similar plasma levels of molsidomine and SIN-1 were found at day 1 and day 21. Correlations between plasma levels of SIN-1 and ST-segment depression were not significant, neither between plasma levels of molsidomine sr and ST-depression. In conclusion no development of tolerance was found after a 3-week period of treatment with 8 mg molsidomine in a slow release formulation given twice a day.