Anti-ischemic and anti-anginal effects of controlled-release and conventional isosorbide-5-mononitrate in stable angina pectoris.

BACKGROUND: A controlled-release formulation of isosorbide-5-mononitrate (5-ISMN) can be administered once daily to lower the peak plasma concentration of 5-ISMN to avoid peak-related side-effects, prolong duration of action and produce predictable and reproducible plasma concentrations of 5-ISMN. This study was undertaken to compare the anti-anginal and anti-ischemic efficacy of controlled-release 5-ISMN 60 mg administered once daily and conventional 5-ISMN 20 mg given twice daily in patients with stable angina pectoris. METHODS: In 44 patients with stable angina pectoris, controlled-release 5-ISMN and the conventional formulation of 5-ISMN were tested in an open, randomized, cross-over study. The study started with a one-week run-in period, during which nitrates were withdrawn. Patients were then randomly allocated to two-week treatment with controlled-release 5-ISMN 60 mg each morning followed by a one-week placebo washout and then a two-week treatment with the conventional formulation of 5-ISMN 20 mg twice daily, or vice versa. Treadmill exercise testing was performed at the end of the placebo run-in and washout periods and at the end of both active treatment periods. RESULTS: Thirty-nine patients completed the study and were included in the statistical evaluation. Total exercise duration and time to appearance of 1-mm ST depression increased significantly after two weeks of treatment with both drugs compared with placebo. However, the time to onset of chest pain increased significantly only after therapy with controlled-release 5-ISMN. Moreover, controlled-release 5-ISMN produced a more pronounced improvement in total exercise duration than the conventional formulation of 5-ISMN after two weeks of therapy. Adverse events were reported by five (13%) patients receiving controlled-release 5-ISMN and by the same percentage of patients receiving conventional 5-ISMN therapy; most of these events were headache and/or dizziness. CONCLUSIONS: Treatment with 5-ISMN in the controlled-release formulation of 60 mg administered once daily appears more effective in improving total exercise duration and increasing the time to onset of chest pain than the conventional formulation of 5-ISMN in patients with stable angina pectoris. Once-daily administration of controlled-release 5-ISMN is well tolerated and convenient.