Plasma endothelin in congestive heart failure: effect of the ACE inhibitor, fosinopril

OBJECTIVES: The study evaluates the influence of treatment with the angiotensin-converting enzyme inhibitor, fosinopril, on the plasma endothelin level in patients with congestive heart failure, and the relationship between plasma endothelin and clinical study parameters (bicycle exercise test, echocardiography, heart failure score and blood pressure). METHODS: Plasma endothelin was measured in 34 patients with moderately severe congestive heart failure at randomisation in the fosinopril/placebo-controlled study 'Fosinopril Efficacy and Safety Trial' and at the end of the 12-week study period. RESULTS: The patients had elevated pre-treatment plasma endothelin concentrations (3.5 +/- 1.2 pg/ml, mean +/- s.d., n = 34) compared with healthy volunteers (2.0 +/- 0.4 pg/ml, n = 21, P < 0.0001). Treatment with fosinopril for 12 weeks lowered plasma endothelin from 3.5 +/- 1.2 to 2.5 +/- 0.7 pg/ml (m = 18, P < 0.005), in contrast to the non-significant increase in the placebo-treated group 3.5 +/- 1.3 to 4.3 +/- 2.4 pg/ml, n = 16). A multiple regression analysis for baseline study parameters, demonstrated a significant relationship between plasma endothelin and exercise test duration and a composite heart failure score classification (r = 0.53, P < 0.001). CONCLUSIONS: Treatment of patients with congestive heart failure with the angiotensin-converting enzyme inhibitor, fosinopril, reduce the elevated plasma endothelin level to normal values. The relation between plasma endothelin and clinical parameters indicates that endothelin may play a pathophysiological role in the progression of congestive heart failure.