Efficacy and safety of controlled-release isosorbide-5-mononitrate in Japanese patients with stable effort angina pectoris.

Abstract:

: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.

journal_name

Int Heart J

authors

Shimada K,Sunayama S,Nakazato K,Satoh H,Kusama Y,Kawakubo K,Daida H

doi

10.1536/ihj.47.695

subject

Has Abstract

pub_date

2006-09-01 00:00:00

pages

695-705

issue

5

eissn

1349-2365

issn

1349-3299

pii

JST.JSTAGE/ihj/47.695

journal_volume

47

pub_type

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