CLINICAL COMPARISON OF ANTIISCHEMIC EFFICACY OF ISOSORBIDE DINITRATE AND MOLSIDOMINE

In 16 patients with documented coronary artery disease, the extent and duration of acute antiischemic and hemodynamic effects of monotherapi es with 120 mg of sustained-release isosorbide dinitrate once daily an d 8 mg of sustained-release molsidomine 3 times daily were compared ac cording to a randomized, double-blind, cross-over and placebo-controll ed protocol including exercise testing for assessment of ST-segment de pression (ST down arrow) at an identical workload and determination of plasma concentrations of both substances. Up to 8 h after dosing in t he morning, more marked and sustained effects were observed with the n itrate (ST down arrow at 2 h, -82%; p < 0.001; at 8 h, -64%; p < 0.01) than with molsidomine (2 h, -68%; p < 0.001; at 8 h, -9%; NS). At 12 h, no more meaningful actions were detectable with isosorbide dinitrat e (-13%, NS) despite plasma concentrations still within a range otherw ise considered therapeutically effective, whereas with molsidomine, at 4 h after renewed dosing, this parameter was reduced by 38% (p < 0.01 ). However, therapeutic coverage over a 24-h period could be demonstra ted on neither regimen, in the case of the nitrate because of the deve lopment of early tolerance, and in the case of molsidomine with its me aningfully shorter half-life because of the necessity of increasing th e dosing frequency even further. No meaningful adverse effects were ob served with either regimen. Nonresponders, overall a minority on one t reatment, responded completely to the alternative regimen and vice ver sa.