Angiotensin-converting enzyme inhibitors improve long-term survival in patients with
left ventricular dysfunction after a
myocardial infarction, but their mechanism of action is not entirely clear. The neurohormonal effects may be important in this respect, as well as an early hemodynamic unloading induced by these drugs. The primary objective was to assess the effect of
trandolapril on plasma levels of
atrial natriuretic peptide. A secondary objective was to assess the effects of
trandolapril on selected
neurohormones, vasoactive
peptides and
enzymes, which may be important in the development of
left ventricular remodeling and
heart failure following an acute
myocardial infarction. A total of 119 patients with an acute
myocardial infarction and a wall motion index < or =1.2 (16-segment echocardiographic model) were randomized to double blind treatment with
trandolapril or placebo within 3-7 days after the onset of
infarction. Blind treatment was discontinued 21 days after the index
infarction. Venous blood samples were collected at rest, before randomization and on the day
after treatment was discontinued. At the end of the study, there were no differences in plasma levels of
atrial natriuretic peptide between the two treatment groups.
Angiotensin-converting enzyme activity was suppressed and plasma
renin activity was higher in the
trandolapril group. No differences in plasma levels of N-terminal pro-
atrial natriuretic peptide,
brain natriuretic peptide,
aldosterone,
noradrenaline,
adrenaline,
vasopressin,
big endothelin-1 and
neuropeptide Y were found between the two treatment groups. There were positive correlations between several markers of neurohormonal activation at baseline and variables expressing
left ventricular dysfunction and clinical
heart failure. Neurohormonal activation is related to
left ventricular dysfunction. The effects of 2-3 weeks of
angiotensin-converting enzyme inhibition on neurohormonal activation does not predict the already established beneficial long-term effects after
myocardial infarction. Thus, early modulation of circulatory
neurohormone levels may not be a major mechanism for the efficacy of
angiotensin-converting enzyme inhibitors in these patients. Selected plasma
hormone markers may still be used to identify patients who might get the greatest benefit from treatment.