EFFECT OF LONG-TERM ENALAPRIL THERAPY ON NEUROHORMONES IN PATIENTS WITH LEFT-VENTRICULAR DYSFUNCTION

The aim of this study was to compare the long-term effects of treatmen t with enalapril or placebo on plasma neurohormones in patients with l eft ventricular (LV) dysfunction. Elevated neurohormonal levels are as sociated with increased mortality in patients with congestive heart fa ilure. Multiple studies have shown that angiotensin-converting enzyme inhibitors decrease mortality and morbidity in and morbidity in these patients. In Studies of Left Ventricular Dysfunction (SOLVD), enalapri l significantly reduced mortality in patients with symptomatic LV dysf unction (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 exami ned in 333 prevention trial and 129 treatment trial patients. Plasma n orepinephrine (NE) and plasma renin activity were measured in these pa tients at baseline, and at 4 and 12 months of follow-up. In a subset o f these patients, atrial natriuretic peptide (ANP) and arginine vasopr essin were also measured. Analysis of covariance models were used to d etermine the effect of enalapril on each neurohormone. Participants in the treatment trial had significantly higher neurohormonal levels whe n compared with those in the prevention trial or normal control subjec ts. In the treatment trial, patients taking enalapril had a greater de crease in plasma NE levels than patients taking placebo (p <0.08). The effect of enalapril on plasma NE was highly significant only in patie nts with high plasma NE levels at baseline, a reduction at 4 months (t he difference between the slopes of regression lines for placebo [0.46 ] vs enalapril [-0.03] was significant at p <0.0095) anti 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, e nalapril 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 pre vention trial patients, enalapril had no significant effect. Because p revious studies suggest that high plasma NE and ANP levels were associ ated with adverse clinical outcomes, the ability of enalapril to decre ase the levels of these neurohormones in patients with symptomatic LV dysfunction may be associated with its clinically beneficial effects.