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

Thirty-seven patients with chronic, stable angina pectoris wereincluded in a randomized, double-blind cross-over study to assessthe efficacy of once- and twice-daily dosage regimens of 60mg isosorbide-5-mononitrate, in a controlied release formulation(5-ISMN Durules^® Astra). After 2 weeks of treatment, duringa symptom-limited bicycle ergometer exercise test performed3 h after the dose, the time to 1 mm ST segment depression wasobserved to be longer by once-daily than by a twice-daily dosageregimen (614 ± 165 vs 561 ± 148 s, P<0·01).The time to the end of exercise was also significantly prolongedby 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 dosageregimens still had a significant effect on the prolongationof the time to onset of angina 9 h after the dose: 420 ±164 s by placebo, 492 ± 161 s by once-daily dosage; P<0·01and 466 ± 154 s by twice-daily dosage; P<0·05.Anginal attack rate and nitroglycerin consumption was significantlylower during the once-daily dosage period as compared with placebo;this difference was not evident during the twice-daily administrationof the drug. Controlled-release 5-ISMN 60 mg given once daily was effectivein angina pectoris patients for at least 9 h after the doseand showed no clinical signs of tolerance after 2 weeks of thetreatment. Attenuation of the clinical effect was observed withthe twice-daily (in 12 h intervals) dosage regimen, presumablycaused by constantly high 5-ISMN plasma concentration.