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.
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.
Nordlander
R
R
Department of Cardiology, Karolinska Hospital, Stockholm, Sweden.
Walter
M
M
D000704:Analysis of Variance; D000787:Angina Pectoris / Q000188:drug therapy* / Q000453:epidemiology; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005080:Exercise Test; D005260:Female; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000627:therapeutic use
D003692:Delayed-Action Preparations; D014665:Vasodilator Agents; D005996:Nitroglycerin; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate