Effect of long-term enalapril therapy on neurohormones in patients with left ventricular dysfunction

Abstract

The aim of this study was to compare the long-term effects of treatment with enalapril or placebo on plasma neurohormones in patients with left ventricular (LV) dysfunction. Elevated neurohormonal levels are associated with increased mortality in patients with congestive heart failure. Multiple studies have shown that angiotensin-converling enzyme inhibitors decrease mortality and morbidity in these patients. In Studies of Left Ventricular Dysfunction (SOLVD), enalapril significantly reduced mortality in patients with symptomatic LV dysfunction (treatment trial). In contrast, in patients with asymptomatic LV dysfunction (prevention trial), there was no significant reduction in mortality with enalapril therapy. The effect of enalapril was examined in 333 prevention trial and 129 treatment trial patients. Plasma norepinephrine (NE) and plasma renin activity were measured in these patients at baseline, and at 4 and 12 months of follow-up. In a subset of these patients, atrial natriuretic peptide (ANP) and arginine vasopressin were also measured. Analysis of covariance models were used to determine the effect of enalapril on each neurohormone. Participants in the treatment trial had significantly higher neurohormonal levels when compared with those in the prevention trial or normal control subjects. In the treatment trial, patients taking enalapril had a greater decrease in plasma NE levels than patients taking placebo (p < 0.08). The effect of enalapril on plasma NE was highly significant only in patients with high plasma NE levels at baseline, witn a reduction at 4 months (the difference between the slopes of regression lines for placebo [0.46] vs enalapril [−0.03] was significant at p < 0.0095) and at 12 months (the difference between the slopes of regression lines for placebo [0.88] vs enalapril [0.02] was significant at p < 0.0006). Furthermore, enalapril also decreased ANP level at 4 months (p < 0.05) and at 1 year (p < 0.05) of follow-up, irrespective of the baseline value. In the prevention trial patients, enalapril had no significant effect. Because previous studies suggest that high plasma NE and ANP levels were associated with adverse clinical outcomes, the ability of enalapril to decrease the levels of these neurohormones in patients with symptomatic LV dysfunction may be associated with its clinically beneficial effects.