Once- versus twice-daily administration of controlled-release isosorbide-5-mononitrate 60 mg in the treatment of stable angina pectoris. A randomized, double-blind, cross-over study. The Swedish Multicentre Group

Abstract

Thirty-seven patients with chronic, stable angina pectoris were included in a randomized, double-blind cross-over study to assess the efficacy of once- and twice-daily dosage regimens of 60 mg isosorbide-5-mononitrate, in a controlled-release formulation (5-ISMN Durules, Astra). After 2 weeks of treatment, during a symptom-limited bicycle ergometer exercise test performed 3 h after the dose, the time to 1 mm ST segment depression was observed to be longer by once-daily than by a twice-daily dosage regimen (614 +/- 165 vs 561 +/- 148 s; P < 0.01). The time to the end of exercise was also significantly prolonged by once-daily dosage, as compared with placebo (693 +/- 158 and 645 +/- 173 s, respectively; P < 0.05), which was not observed with the twice-daily regimen. Both dosage regimens still had a significant effect on the prolongation of the time to onset of angina 9 h after the dose: 420 +/- 164 s by placebo, 492 +/- 161 s by once-daily dosage; P < 0.01, and 466 +/- 154 s by twice-daily dosage; P < 0.05. Anginal attack rate and nitroglycerin consumption was significantly lower during the once-daily dosage period as compared with placebo; this difference was not evident during the twice-daily administration of the drug. Controlled-release 5-ISMN 60 mg given once daily was effective in angina pectoris patients for at least 9 h after the dose and showed no clinical signs of tolerance after 2 weeks of the treatment. Attenuation of the clinical effect was observed with the twice-daily (in 12 h intervals) dosage regimen, presumably caused by constantly high 5-ISMN plasma concentration.