Effects of enalapril, candesartan or both on neurohumoral activation and LV volumes and function in patients with heart failure not treated with a beta-blocker.
BACKGROUND
The long-term effects of the angiotensin-receptor blocker candesartan, the angiotensin-converting enzyme inhibitor enalapril or their combination have been incompletely studied in a large cohort of patients with heart failure not treated with beta-blockers. The objective of this study was to investigate the changes in neurohormones and LV volumes and ejection fraction in patients treated with enalapril, candesartan, or enalapril plus candesartan without concomitant beta-blocker therapy.


METHODS
Three hundred and ninety-two patients from the RESOLVD pilot study not treated with a beta-blocker at baseline or at any time during the trial were analyzed. Norepinephrine, endothelin-1, big endothelin-1, angiotensin-II, aldosterone, N-terminal proANP, BNP, and radionuclide angiography were measured before and after 43 weeks of treatment with candesartan alone (n = 162), or enalapril alone (n = 45), or candesartan plus enalapril (n = 185). Endpoints were assessed at baseline and after 43 weeks of therapy.


RESULTS
LV end-diastolic and end-systolic volumes increased significantly at 43 weeks in all groups except for patients treated with enalapril plus candesartan. BNP decreased at 43 weeks only in patients receiving dual angiotensin-II suppression (-6.1 +/- 37.8 pmol/l). Angiotensin-II levels were significantly increased in patients treated with candesartan (+23.6 +/- 47.1 pg/ml; p<0.05).


CONCLUSIONS
We conclude that angiotensin-II modulation, with enalapril and candesartan, without concomitant utilization of beta-blocker lead to a decrease in BNP and an attenuation of the increase in LV end-diastolic and end-systolic volumes without a reversal of this process in the long term.
White
Michel
M
Research Center, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada. m_white@icm-mhi.com
Rouleau
Jean-Lucien
JL
Afzal
Rizwan
R
Floras
John
J
Yusuf
Salim
S
McKelvie
Robert S
RS
D000368:Aged; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood / Q000187:drug effects; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage*; D019332:Endothelin-1 / Q000097:blood / Q000187:drug effects; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000187:drug effects; D009638:Norepinephrine / Q000097:blood; D010446:Peptide Fragments / Q000097:blood / Q000187:drug effects; D011875:Radionuclide Angiography; D013318:Stroke Volume / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D019332:Endothelin-1; D010446:Peptide Fragments; D013777:Tetrazoles; C109794:pro-brain natriuretic peptide (1-76); D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D000450:Aldosterone; D004656:Enalapril; C081643:candesartan; D009638:Norepinephrine