CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved
Purpose
To determine whether the angiotensin II receptor blocker candesartan is beneficial in patients with chronic heart failure (CHF) and preserved left ventricular systolic function
Reference
Yusuf S, Pfeffer MA, Swedberg K, et al. for the CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved trial. Lancet 2003;362:777–81.
CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved - TRIAL DESIGN -
Design
Multicenter, multinational, randomized, double-blind, placebo-controlled
Patients
3023 patients aged >18 years with symptomatic CHF (NYHA class II–IV), who had left ventricular ejection fraction >40%
Follow up and primary endpoint
Primary endpoint: cardiovascular death or hospital admission for CHF. Median 36.6 months follow up.
Treatment
Placebo or candesartan titrated to 32 mg once daily
CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved - TRIAL DESIGN continued-
Age (years)a
Male
NYHA class:
II
III
IV
LVEF
41–49%
50–59%
>60%
BP (mmHg)a
Systolic
Diastolic
History
MI
Diabetes mellitus
Hypertension
Baseline characteristics (%)
Yusuf et al. Lancet 2003;362:777–81.
aMean
Medications
ACE inhibitor
Beta-blocker
Spironolactone
Aspirin
Lipid-lowering drug
Heart failure cause
Ischemic
Idiopathic
Hypertensive
CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved - RESULTS -
Nonsignificant trend to reduction in primary outcome of cardiovascular death or hospital admission for CHF in candesartan group compared with placebo (22 vs. 24.3%, P=0.118)
Secondary outcomes – composites of primary outcome and MI, nonfatal stroke and coronary revascularization – also showed nonsignificant trend
Total number of hospital admissions for CHF significantly reduced in candesartan group (402 vs. 566, P=0.014)
All-cause mortality similar in both groups (244 vs. 237 patients)
Permanent discontinuation due to adverse event or laboratory abnormality more frequent with candesartan (17.8 vs. 13.5%, P=0.001)
CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved - RESULTS continued -
Years after randomization
Proportion
with event
(%)
0
0
1.0
2.0
3.0
3.5
10
20
30
40
50
Cardiovascular death or hospital admission for CHF
Yusuf et al. Lancet 2003;362:777–81.
CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved - RESULTS continued -
P
Cardiovascular death or
hospital admission for CHF
0.89 (0.77–1.03)
0.118
Primary and secondary outcomes
333
No.
(22.0)
(%)
Candesartan
(n=1514)
366
No.
(24.3)
(%)
Placebo
(n=1509)
Hazard ratio
(95% CI)
Yusuf et al. Lancet 2003;362:777–81.
CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved - RESULTS continued -
P
Cause of discontinuation
Discontinuation because of adverse events
No.
(%)
Candesartan
(n=1514)
No.
(%)
Placebo
(n=1509)
Yusuf et al. Lancet 2003;362:777–81.
CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved - SUMMARY -
In patients who had symptomatic CHF and preserved left ventricular systolic function, with candesartan there was no significant reduction of the following, although the trend was favorable:
Cardiovascular death or hospitalization for CHF
Secondary outcomes that combined these with MI, stroke and coronary revascularization procedures
However, the total number of hospital admissions for CHF was significantly reduced in the candesartan group.