Hormonal and renal differences between low dose and high dose angiotensin converting enzyme inhibitor treatment in patients with chronic heart failure.
OBJECTIVE
To assess the differential effects of low dose (5 mg) and high dose (20 mg) lisinopril treatment on cardiovascular hormones, renal function, and blood pressure over 24 hours in patients with heart failure.


METHODS
Double-blind crossover study.


METHODS
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee.


METHODS
19 patients with chronic heart failure and left ventricular ejection fraction < or = 45%.


RESULTS
Plasma concentrations of aldosterone and endothelin were lower on the 20 mg dose (plasma aldosterone mean at peak drug effect: 90.7 v 152.0 pg/ml, P < 0.001; mean at trough effect: 124.7 v 174.4 pg/ml, P < 0.01; plasma endothelin at trough effect 4.70 v 6.04 pmol/l, P = 0.03). Creatinine clearance was lower on 20 mg lisinopril (68.7 v 82.1 ml/min, P < 0.05). The area under the curve for diastolic blood pressure over 24 hours was significantly lower on 20 mg (mean difference 3.0 mm Hg, P = 0.04); for systolic blood pressure there was a similar trend (mean difference 5.7 mmHg, P = 0.05). Plasma concentrations of atrial natriuretic peptide (ANP) and B-type natriuretic peptide were similar for both doses; urinary excretion of ANP was lower on 20 mg (12.2 v 13.6 pmol, P < 0.05).


CONCLUSIONS
These results indicate that within the usual therapeutic range, high doses of lisinopril cause greater suppression of selected cardiovascular hormones than low doses in heart failure, but are associated with lower creatinine clearance in some patients.
Davidson
N C
NC
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee.
Coutie
W J
WJ
Webb
D J
DJ
Struthers
A D
AD
D000450:Aldosterone / Q000097:blood*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000378:metabolism*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D016232:Endothelins / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D017706:Lisinopril / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D016232:Endothelins; D009419:Nerve Tissue Proteins; D020097:Natriuretic Peptide, Brain; C076910:brain natriuretic peptide, porcine; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D003404:Creatinine; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A