PLASMA ENDOTHELIN IN CONGESTIVE-HEART-FAILURE - EFFECT OF THE ACE-INHIBITOR, FOSINOPRIL

Objectives: The study evaluates the influence of treatment with the an giotensin-converting enzyme inhibitor, fosinopril, on the plasma endot helin level in patients with congestive heart failure, and the relatio nship between plasma endothelin and clinical study parameters (bicycle exercise test, echocardiography, heart failure score and blood pressu re), Methods: Plasma endothelin was measured in 34 patients with moder ately severe congestive heart failure at randomisation in the fosinopr il/placebo-controlled study 'Fosinopril Efficacy and Safety Trial' and at the end of the 12-week study period. Results: The patients had ele vated 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 plas ma endothelin from 3.5+/-1.2 to 2.5+/-0.7 pg/ml (n=18, P <0.005), in c ontrast to the non-significant increase in the placebo-treated group ( 3.5+/-1.3 to 4.3+/-2.5 pg/ml, n=16). A multiple regression analysis fo r baseline study parameters, demonstrated a significant relationship b etween plasma endothelin and exercise test duration and a composite he art failure score classification (r=0.53, P <0.001). Conclusions: Trea tment of patients with congestive heart failure with the angiotensin-c onverting enzyme inhibitor, fosinopril, reduce the elevated plasma end othelin level to normal values, The relation between plasma endothelin and clinical parameters indicates that endothelin may play a pathophy siological role in the progression of congestive heart failure.