Efficacy and safety of controlled-release isosorbide-5-mononitrate in Japanese patients with stable effort angina pectoris.
A new controlled-release isosorbide-5-mononitrate (CR-ISMN) preparation has been developed to meet the requirement for a low nitrate concentration interval in order to avoid nitrate tolerance. We conducted a randomized, double-blind, placebo-controlled study in 31 Japanese patients with stable effort angina pectoris to investigate the efficacy and safety of CR-ISMN. Patients were randomly assigned to either CR-ISMN (40 mg once daily) or placebo groups for 2 weeks after two consecutive symptom-limited treadmill exercise tests using the Bruce protocol to ascertain the reproducibility of exercise tolerance during the placebo run-in period. Exercise tests were repeated at 5, 12, and 24 hours after administration on the final day. No significant difference in exercise time to moderate angina was identified between the CR-ISMN and placebo groups at 5, 12, or 24 hours after administration. However, the changes in exercise were prolonged at 5 hours but not shortened at 24 hours in the CR-ISMN group. The results of subgroup analysis suggested that the concomitant use of insulin might lead to confounding results. Although headache was the most frequent adverse effect in the CR-ISMN group, all symptoms were mild and at self-limiting levels. The plasma concentrations of CR-ISMN maintained therapeutic levels at 5 and 12 hours, and gradually decreased to less than the minimum therapeutic concentration (100 ng/mL) at 24 hours after administration. This study demonstrates that CR-ISMN improves exercise tolerance during the daytime and is well-tolerated in Japanese patients with stable effort angina pectoris without increasing the number of serious adverse effects.
Shimada
Kazunori
K
Department of Cardiovascular Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Sunayama
Satoshi
S
Nakazato
Kaoru
K
Satoh
Hiroyuki
H
Kusama
Yoshiki
Y
Kawakubo
Kiyoshi
K
Daida
Hiroyuki
H
D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004361:Drug Tolerance; D005080:Exercise Test; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000097:blood
D003692:Delayed-Action Preparations; D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate