Efficacy of eccentric dosing with sustained-release isosorbide dinitrate in patients with angina pectoris.
OBJECTIVE
To assess the anti-anginal efficacy of eccentric dosing with a sustained-release formulation of isosorbide dinitrate (ISDN) administered twice daily in an eccentric fashion (08:00 and 14:00).


METHODS
A placebo controlled crossover study of 16 patients with chronic stable angina who received, in random order, either placebo or sustained-release ISDN 40 mg twice daily for a period of seven to 10 days. Patients were entered who had reproducible exercise test to the development of moderate angina. All anti-anginal drugs with the exception of beta-blockers were withheld during the study period. The primary end-point was the treadmill walking time to the development of moderate angina.


RESULTS
Patients receiving active therapy showed a significant increase in treadmill walking time to moderate angina over that seen with placebo at 3 and 6 h after the morning dose and 3 and 8 h after the afternoon dose. Similar trends occurred for the time to onset of angina and the time to development of 1 mm of ST segment depression on the electrocardiogram.


CONCLUSIONS
Eccentric dosing with sustained-release ISDN, 40 mg given 6 h apart, provided significant improvement in exercise performance for up to 14 h during sustained therapy.
Department of Medicine, Queen's University, Kingston, Ontario.
J O
JO
Parker
M G
MG
Baird
D000787:Angina Pectoris / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D002908:Chronic Disease; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004562:Electrocardiography; D005080:Exercise Test; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000627:therapeutic use*
D003692:Delayed-Action Preparations; D007548:Isosorbide Dinitrate