ACUTE AND CHRONIC HEMODYNAMIC-EFFECTS OF ENALAPRIL (MK-421) IN CONGESTIVE HEART-FAILURE

Enalapril, a new long-acting angiotensin-converting enzyme inhibitor, was administered orally to 12 patients with stable congestive cardiac failure, NYHA [New York Heart Association] function class III-IV. Acute and chronic hemodynamic effects were evaluated in addition to clinical response. This open pilot study indicated marked reduction of pulmonary capillary wedge pressure from 21.8 .+-. 5.9 mm Hg (mean .+-. 1 SD) - 13.3 .+-. 4.5 mm Hg (P < 0.01) and peripheral resistance from 1837 .+-. 860 dynes .cntdot. s-11 .cntdot. cm-5-1063 .+-. 584 dynes .cntdot. s-1 .cntdot. cm-5 at 6 h (P < 0.01). Well-tolerated hypotension with mean arterial pressure from 88.0 .+-. 11.6 mm Hg - 73.1 .+-. 11.7 mm Hg at 6 h (P < 0.01) was recorded. No significant increase in cardiac output was observed. Angiotensin-converting enzyme activity was powerfully inhibited at the time of peak hemodynamic effect from 25.3 .+-. 9.8 U/ml - 4.9 .+-. 3.4 U/ml (P < 0.01) and sustained, but attenuated reduction at 24 h (8.7 .+-. 4.7 U/ml) was observed. All patients reported subjective improvement and this clinical improvement has been sustained during follow-up from 19-21 mo. although baseline hemodynamic parameters at chronic recatheterization did not demonstrate significant improvement. The pharmacodynamics and toxicity of enalapril as compared to captopril are discussed. The long half-life, toxicity and gradual onset of action represent a clinical advantage with regard to patient therapy.