Anti-ischemic effects of an 80-mg tablet of isosorbide dinitrate in sustained-release form before and after 2 weeks treatment with 80 mg once daily or twice daily

Abstract

The purpose of this study was to investigate whether the anti-ischemic effects of a single 80-mg tablet of isosorbide dinitrate in sustained-release form are attenuated after 2 weeks of twice-daily administration. In order to follow a double-blind protocol with respect to the 12-h interval, we also evaluated, in randomized order, another group of patients receiving the tablets once daily. Parameters for assessment of the anti-ischemic effects were changes in exercise-induced ST-segment depression and the simultaneously recorded left ventricular ejection fraction, as determined by radionuclide ventriculography. The ST-segment depression was measured completely blind; the left ventricular ejection fraction was calculated automatically with a clinically validated software. In the group that received the tablets once daily (n = 10) none of the patients showed any signs of attenuation of the beneficial anti-ischemic effects. However, seven of the 12 patients who received the tablets twice daily demonstrated significant attenuation. Thus, based on analysis of the presently available studies, in order to guarantee maintenance of the anti-ischemic benefits, a once-daily high dose of ISDN in sustained-release form (80 mg or even higher) is recommended.