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Randomized, double-blind, placebo-controlled long-term study of isosorbide-5-mononitrate therapy in patients with
Erik Tingberg1, Anders Roijer, Ulf Thilen
1Department of Cardiology, University Hospital, Lund, Sweden. erik.tingberg@kard.lu.se
Insights
Long-term oral isosorbide-5-mononitrate (IS-5-MN) therapy in chronic heart failure patients after myocardial infarction reduced atrial natriuretic peptide and diuretic use. Less left ventricular dilation occurred in patients with severe dysfunction.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Nitrates are commonly used with other drugs for chronic heart failure (CHF).
- Limited data exist on long-term nitrate effects in post-myocardial infarction (MI) patients with left ventricular (LV) dysfunction on standard therapy.
Purpose of the Study:
- To evaluate the long-term effects of isosorbide-5-mononitrate (IS-5-MN) in patients with LV dysfunction post-MI.
Main Methods:
- A randomized, double-blind, placebo-controlled trial.
- 47 patients received daily IS-5-MN (60 mg) for 11 months; 45 received placebo.
- Patients had clinical or echocardiographic evidence of LV dysfunction post-MI.
Main Results:
- No significant differences in invasive hemodynamics or overall echocardiographic measures.
- IS-5-MN therapy showed less increase in end-diastolic volume index in patients with ejection fraction <=40% (P=.047).
- IS-5-MN significantly reduced atrial natriuretic peptide (P=.002) and diuretic use (P=.02) compared to placebo.
Conclusions:
- Long-term oral IS-5-MN therapy reduced atrial natriuretic peptide and diuretic requirements.
- Less LV dilation was observed in patients with baseline severe LV dysfunction.
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.