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 function class III-IV. Acute and chronic hemodynamic effects were evaluated in addition to clinical response. The results of this open pilot study indicated marked reduction of pulmonary capillary wedge pressure from 21.8 +/- 5.9 mm Hg (mean +/- 1 SD) to 13.3 +/- 4.5 mm Hg (P less than 0.01) and peripheral resistance from 1837 +/- 860 dynes X sec-1 X cm-5 to 1063 +/- 584 dynes X sec-1 X cm-5 at 6 hr (P less than 0.01). Well-tolerated hypotension with mean arterial pressure from 88.0 +/- 11.6 mm Hg to 73.1 +/- 11.7 mm Hg at 6 hr (P less than 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 to 4.9 +/- 3.4 U/ml (P less than 0.01) and sustained, but attenuated reduction at 24 hr (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 to 21 months although baseline hemodynamic parameters at chronic re-catheterization did not demonstrate significant improvement. The pharmacodynamics and toxicity of enalapril as compared to captopril are discussed. The long half-life, low toxicity and gradual onset of action are seen as representing a clinical advantage with regard to patient therapy.
D000368:Aged; D004151:Dipeptides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004656:Enalapril; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012084:Renin-Angiotensin System / Q000187:drug effects
D004151:Dipeptides; D004791:Enzyme Inhibitors; D004656:Enalapril