Randomized, double-blind, placebo-controlled long-term study of isosorbide-5-mononitrate therapy in patients with left ventricular dysfunction after acute myocardial infarction.
BACKGROUND
Nitrates are often administrated with a variety of other pharmacologic agents in the management of chronic heart failure (CHF). However, limited information is available concerning the long-term effects in patients with evidence of left ventricular (LV) dysfunction after acute myocardial infarction (AMI) already treated with standard heart failure therapy.


METHODS
In a randomized, double-blind, placebo-controlled trial, we evaluated the effects of a 60 mg dose of isosorbide-5-mononitrate (IS-5-MN) given daily for 11 months to 47 patients with clinical or echocardiographic evidence of left ventricular dysfunction after acute myocardial infarction. Forty-five patients received a placebo.


RESULTS
Invasive hemodynamic measurements did not show any difference between the treatment regimens. Overall changes in echocardiographic measurements were not significantly different between IS-5-MN therapy and the placebo groups. However, in a prespecified subgroup with left ventricular ejection fraction < or =40% at baseline, IS-5-MN therapy resulted in a lesser increase of end-diastolic volume index than the placebo (P =.047). IS-5-MN significantly reduced the serum concentration of atrial natriuretic peptide (mean 20.0 pmol/L, 95% CI 7.7-32.3, P =.002), whereas the placebo did not (P =.041 for the difference between the groups). The proportion of patients taking diuretics was significantly reduced in the IS-5-MN group, from 30 of 44 to 20 of 44 (P =.02), but not with placebo, which remained at 27 of 43 (P = 1.0, with P =.048 for the difference between the regimens).


CONCLUSIONS
Oral, long-term IS-5-MN therapy resulted in lower atrial natriuretic peptide levels and reduced the need for additional diuretics. Less LV dilatation was observed in patients with more severe LV dysfunction at baseline.
Tingberg
Erik
E
Department of Cardiology, University Hospital, Lund, Sweden. erik.tingberg@kard.lu.se
Roijer
Anders
A
Thilen
Ulf
U
Eskilsson
Jan
J
Ohlin
Hans
H
D000368:Aged; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D003692:Delayed-Action Preparations; D004232:Diuretics / Q000008:administration & dosage; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004452:Echocardiography; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications*; D010446:Peptide Fragments / Q000378:metabolism; D017257:Ramipril / Q000008:administration & dosage; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology
D003692:Delayed-Action Preparations; D004232:Diuretics; D010446:Peptide Fragments; C074733:ANF (4-28), Leu(8,18)-Ile(12)-Ala(20)-MePhe(26)-Tyr(28)-Pro(29)-; D009320:Atrial Natriuretic Factor; D007548:Isosorbide Dinitrate; D017257:Ramipril; C030397:isosorbide-5-mononitrate