Acute and 3-month treatment effects of candesartan cilexetil on hemodynamics, neurohormones, and clinical symptoms in patients with congestive heart failure.
BACKGROUND
This study evaluated the short-term and long-term effects of the angiotensin II type 1 receptor antagonist candesartan cilexetil on hemodynamics, neurohormones, and clinical symptoms in patients with congestive heart failure (CHF).


METHODS
In this multicenter, double-blind, parallel-group study, 218 patients with CHF (New York Heart Association class II or III) with impaired left ventricular function (ejection fraction < or =40%) and pulmonary capillary wedge pressure > or =13 mm Hg were randomly assigned to 12 weeks of treatment with placebo (n = 44) or candesartan cilexetil (2 mg [n = 45], 4 mg [n = 46], 8 mg [n = 39], or 16 mg [n = 44]) once daily after a 2-week placebo run-in period. Hemodynamic measurements were performed by right heart catheterization over a 24-hour period after single (day 1) and repeated (3-month) treatment with the study drug.


RESULTS
On regression analysis of the time-response curves, single and multiple doses of candesartan cilexetil produced sustained, significant, and dose-dependent reductions in pulmonary capillary wedge pressure (short-term effect P =.036, long-term effect P =.035) and mean pulmonary arterial pressure (short-term effect P =.031, long-term effect P =.042). Systemic vascular resistance showed a trend toward decreasing with dose on short-term and long-term treatments. No consistent changes were seen in cardiac index. Compensatory increases in plasma renin activity and angiotensin II levels with decreases in aldosterone and atrial natriuretic peptide were dose-dependent and significant. Candesartan cilexetil improved clinical symptoms, stabilized patient New York Heart Association status compared with placebo, and was judged to be an efficacious treatment by the investigators. More patients receiving placebo stopped the trial prematurely because of an adverse event than in any candesartan cilexetil group, and there was no excess of deaths in any treatment group. Candesartan was safe and well tolerated at all dosages.


CONCLUSIONS
Candesartan cilexetil demonstrated significant short-term and long-term improvements in hemodynamic, neurohormonal, and symptomatic status and was well tolerated in patients with CHF.
Mitrovic
V
V
Kerckhoff-Klinik der Max-Planck-Gesellschaft, Bad Nauheim, Germany. Veselin.Mitrovic@kerckhoff.med.uni-giessen.de
Willenbrock
R
R
Miric
M
M
Seferovic
P
P
Spinar
J
J
Dabrowski
M
M
Kiowski
W
W
Marks
D S
DS
Alegria
E
E
Dukát
A
A
Lenz
K
K
Arens
H A
HA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D057911:Angiotensin Receptor Antagonists; D009320:Atrial Natriuretic Factor / Q000097:blood; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects*; D006728:Hormones / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011355:Prodrugs / Q000494:pharmacology / Q000627:therapeutic use; D012044:Regression Analysis; D012083:Renin / Q000097:blood; D013777:Tetrazoles; D016896:Treatment Outcome
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D006728:Hormones; D010919:Placebos; D011355:Prodrugs; D013777:Tetrazoles; D000804:Angiotensin II; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012083:Renin; C077793:candesartan cilexetil