Aldosterone receptor antagonism induces reverse remodeling when added to angiotensin receptor blockade in chronic heart failure.
OBJECTIVE
The objective of this study was to determine if adding spironolactone to an angiotensin II receptor blocker improves left ventricular (LV) function, mass, and volumes in chronic heart failure.


BACKGROUND
Add-on spironolactone therapy substantially improves clinical outcomes among patients with severe heart failure (HF) on standard therapy. However, the value of combining spironolactone with an angiotensin II receptor blocker on LV reverse remodeling in mild-to-moderate systolic HF is unclear.


METHODS
Fifty-one systolic HF patients with left ventricular ejection fraction (LVEF) <40% were randomly assigned to receive 1-year treatment of candesartan and spironolactone (combination group) or candesartan and placebo (control group). Reverse remodeling was assessed by serial cardiac magnetic resonance imaging and echocardiographic tissue Doppler imaging (TDI).


RESULTS
There were significant improvements in LVEF (35 +/- 3% vs. 26 +/- 2%, p < 0.01) and reduction of LV end-diastolic volume index (121 +/- 16 ml/m2 vs. 155 +/- 14 ml/m2, p = 0.001), end-systolic volume index (88 +/- 17 ml/m2 vs. 120 +/- 15 ml/m2, p < 0.0005), and LV mass index (81 +/- 6 g/m2 vs. 93 +/- 6 g/m2, p = 0.002) in the combination group at 1 year. In addition, there was significant increase in peak basal systolic velocity and strain by TDI, decrease in index of filling pressure, and increase in cyclic variation integrated backscatter. In the control group, there were no significant changes in all these parameters after 1 year.


CONCLUSIONS
The addition of spironolactone to candesartan has significant beneficial effects on LV reverse remodeling in patients with mild-to-moderate chronic systolic HF.
Chan
Anna K Y
AK
Division of Cardiology, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.
Sanderson
John E
JE
Wang
Tian
T
Lam
Wynnie
W
Yip
Gabriel
G
Wang
Mei
M
Lam
Yat-Yin
YY
Zhang
Yan
Y
Yeung
Leata
L
Wu
Eugene B
EB
Chan
Wilson W M
WW
Wong
John T H
JT
So
Nina
N
Yu
Cheuk-Man
CM
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage*; D011446:Prospective Studies; D013148:Spironolactone / Q000008:administration & dosage*; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome; D014463:Ultrasonography; D020257:Ventricular Remodeling / Q000187:drug effects*
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D000451:Mineralocorticoid Receptor Antagonists; D013777:Tetrazoles; D013148:Spironolactone; C081643:candesartan