CHARM-Overall: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Overall
Purpose
To determine whether the angiotensin II receptor blocker candesartan reduces all-cause mortality in patients with chronic heart failure (CHF)
Reference
Pfeffer MA, Swedberg K, Granger CB, et al. for the CHARM Investigators and Committees. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 2003;362:759–66.
CHARM-Overall: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Overall - TRIAL DESIGN -
Design
Combined data from three parallel multicenter, multinational, randomized, double-blind, placebo-controlled trials
Patients
7599 patients aged >18 years with symptomatic CHF (NYHA class II–IV) and:
left ventricular ejection fraction (LVEF) <40%, receiving an ACE inhibitor (2548: CHARM-Added trial) or
LVEF <40%, but not receiving an ACE inhibitor because of previous intolerance (2028: CHARM-Alternative trial) or
LVEF >40% (3023: CHARM-Preserved trial)
Follow up and primary endpoint
Primary endpoint: all-cause mortality. Mean 37.7 months follow up.
Treatment
Placebo or candesartan titrated to 32 mg once daily
CHARM-Overall: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Overall - TRIAL DESIGN continued-
Age (years)a
Male
NYHA class:
LVEF
Systolic BP (mmHg)a
II
III
IV
<30%
>30–39
>40–49
>50%
History
MI
Diabetes mellitus
Hypertension
Medications
ACE inhibitor
Beta-blocker
Spironolactone
Aspirin
Lipid-lowering drug
Baseline characteristics (%)
Pfeffer et al. Lancet 2003;362:759–66.
aMean
53
28
55
41
55
17
56
42
Placebo
(n=3796)
Candesartan
(n=3803)
CHARM-Overall: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Overall - RESULTS -
All-cause mortality reduction in candesartan and placebo groups of borderline significance (23 vs. 25%, hazard ratio 0.91, 95% CI 0.83–1.00, P=0.055)
Cardiovascular death significantly reduced (18.2 vs. 20.3%, P=0.012). Noncardiovascular death not significantly different (P=0.45)
Combined endpoint of cardiovascular death or hospital admission for CHF significantly reduced (30.2 vs. 34.5%, P<0.0001)
Hospital admission for CHF significantly reduced (19.9 vs. 24.2%, hazard ratio 0.79, 95% CI 0.72–0.087, P <0.0001)
Permanent discontinuation due to adverse event or laboratory abnormality more frequent with candesartan (21 vs. 16.7%, P<0.0001)
CHARM-Overall: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Overall - RESULTS continued -
Years after randomization
Mortality
(%)
0
0
1.0
2.0
3.0
3.5
5
10
15
20
25
30
All-cause mortality
Pfeffer et al. Lancet 2003;362:759–66.
CHARM-Overall: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Overall - RESULTS continued -
Years after randomization
0
0
1.0
2.0
3.0
3.5
10
20
30
40
50
Cardiovascular death or hospital admission for CHF
Pfeffer et al. Lancet 2003;362:759–66.
Proportion
with event
(%)
CHARM-Overall: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Overall - SUMMARY -
In patients with symptomatic CHF, candesartan:
Tended to reduce overall mortality
Reduced:
Cardiovascular death
Hospital admission due to CHF
Benefit was independent of left ventricular ejection fraction and concurrent ACE inhibitor