Effect of candesartan on cause-specific mortality in heart failure patients: the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) program.
BACKGROUND
Patients with heart failure are at increased risk of sudden death and death attributed to progressive pump failure. We assessed the effect of candesartan on cause-specific mortality in patients enrolled in the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) program.


RESULTS
The CHARM program consisted of 3 component trials that enrolled patients with symptomatic heart failure: CHARM-Alternative (n=2028; LVEF<=40% [corrected] and ACE intolerant), CHARM-Added (n=2548; LVEF<=40%, [corrected] already on ACE inhibitors), and CHARM-Preserved (n=3023; LVEF >40%). Patients were randomized to candesartan, titrated to 32 mg QD, or placebo and were followed up for a median of 37.7 months. All deaths were reviewed by a blinded adjudication committee and categorized according to prespecified definitions on the basis of a narrative and source documentation. The number and rate of deaths by cause were calculated for each of the component trials and the overall program. Of all the patients, 8.5% died suddenly, and 6.2% died of progressive heart failure. Candesartan reduced both sudden death (HR 0.85 [0.73 to 0.99], P=0.036) and death from worsening heart failure (HR 0.78 [0.65 to 0.94], P=0.008). These reductions were most apparent in the patients with LVEF<=40% [corrected].


CONCLUSIONS
Candesartan reduced sudden death and death from worsening heart failure in patients with symptomatic heart failure, although this reduction was most apparent in patients with systolic dysfunction.
Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, Mass 02445, USA. ssolomon@rics.bwh.harvard.edu
Scott D
SD
Solomon
Duolao
D
Wang
Peter
P
Finn
Hicham
H
Skali
Leonardo
L
Zornoff
John J V
JJ
McMurray
Karl
K
Swedberg
Salim
S
Yusuf
Christopher B
CB
Granger
Eric L
EL
Michelson
Stuart
S
Pocock
Marc A
MA
Pfeffer
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D002170:Canada / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000401:mortality* / Q000517:prevention & control; D002423:Cause of Death; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000517:prevention & control; D018450:Disease Progression; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D016037:Single-Blind Method; D013548:Sweden / Q000453:epidemiology; D013777:Tetrazoles / Q000627:therapeutic use*; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D018487:Ventricular Dysfunction, Left / Q000401:mortality / Q000517:prevention & control
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan