Efficacy and tolerability of adding an angiotensin receptor blocker in patients with heart failure already receiving an angiotensin-converting inhibitor plus aldosterone antagonist, with or without a beta blocker. Findings from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Added trial.
BACKGROUND
The efficacy and safety of adding an angiotensin receptor blocker (ARB) in heart failure (HF) patients already taking an angiotensin-converting enzyme-inhibitor (ACE-I) plus an aldosterone antagonist is uncertain (especially if taking a beta blocker as well). The CHARM-Added trial describes the largest experience of using multiple inhibitors of the renin-angiotensin-aldosterone system (RAAS) together.


RESULTS
2548 HF patients, taking an ACE-I (936 no spironolactone/no beta blocker; 1175 no spironolactone/beta blocker; 199 spironolactone/no beta blocker; 238 sprionolactone/beta blocker), were randomized to placebo or candesartan and followed for 41 months (median). The primary outcome was cardiovascular death or HF hospitalization. In patients taking both a beta blocker and spironolactone (in addition to an ACE-I) at baseline, the candesartan:placebo hazard ratio was 0.85(95% CI 0.56, 1.29), compared to 0.85(95% CI 0.75, 0.96) in all randomized patients (interaction p value 0.49). The relative risk of discontinuation of candesartan (compared to placebo) because of hypotension, increased serum creatinine or hyperkalemia was not increased in patients taking spironolactone at baseline.


CONCLUSIONS
An ARB may provide added benefit, at acceptable risk, in HF patients already taking spironolactone as well as an ACE-I and beta blocker. These findings must be confirmed in a prospective randomized trial before this approach can be recommended, routinely.
Weir
R A P
RA
Department of Cardiology, Western Infirmary, Glasgow, G11 6NT, United Kingdom; Faculty of Medicine, University of Glasgow, United Kingdom.
McMurray
John J V
JJ
Puu
Margareta
M
Solomon
Scott D
SD
Olofsson
Bertil
B
Granger
Christopher B
CB
Yusuf
Salim
S
Michelson
Eric L
EL
Swedberg
Karl
K
Pfeffer
Marc A
MA
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D003404:Creatinine / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D006947:Hyperkalemia / Q000453:epidemiology; D007022:Hypotension / Q000453:epidemiology; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D012189:Retrospective Studies; D013148:Spironolactone / Q000627:therapeutic use*; D013777:Tetrazoles / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D000451:Mineralocorticoid Receptor Antagonists; D013777:Tetrazoles; D013148:Spironolactone; D003404:Creatinine; C081643:candesartan