1. 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.

2. 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

3. CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved - TRIAL DESIGN continued-
Baseline characteristics (%)
67.1
136.3
77.8 59 60 39 1 36 34 31
Placebo
(n=1509)
67.2
136.0
77.8 61 62 37 2 35 36 29
Candesartan
(n=1514) 44 28 64
Placebo
(n=1509) 19 56 12 59 43 57 9 23 45 29 65 20 56 11 58 41 9 22
Candesartan
(n=1514)
Age (years)a
History MI
Male
Diabetes mellitus
NYHA class:
Hypertension II
Heart failure cause
III
Ischemic IV
Idiopathic
LVEF
Hypertensive
41–49%
Medications
50–59%
ACE inhibitor
>60%
Beta-blocker
BP (mmHg)a
Spironolactone
Systolic
Aspirin
Diastolic
Lipid-lowering drug
aMean
Yusuf et al. Lancet 2003;362:777–81.

4. 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)

5. CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved - RESULTS continued -
Cardiovascular death or hospital admission for CHF
Proportion 50
with event
Placebo
Candesartan
(%) 40 30
Hazard ratio 0.89
(95% CI 0.77–1.03)
P = 0.118 20 10
1.0
2.0
3.0
3.5
Years after randomization
Yusuf et al. Lancet 2003;362:777–81.

6. CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved - RESULTS continued -
Primary and secondary outcomes
Placebo
Candesartan
(n=1509)
(n=1514)
Hazard ratio P
(95% CI)
No.
(%)
No.
(%)
Cardiovascular death or
366
(24.3)
333
(22.0)
0.89 (0.77–1.03)
0.118
hospital admission for CHF
Cardiovascular death
0.99 (0.80–1.22)
0.918
170
(11.2)
(11.3)
Hospital admission for CHF
0.85 (0.72–1.01)
0.072
241
(15.9)
276
(18.3)
Cardiovascular death, hospital
admission for CHF, or MI
0.90 (0.78–1.03)
0.126
365
(24.1)
399
(26.4)
Cardiovascular death, hospital
admission for CHF, MI,
or stroke
0.88 (0.77–1.01)
0.078
388
(25.6)
429
(28.4)
Cardiovascular death, hospital
admission for CHF, MI, stroke,
or coronary revascularization
0.91 (0.80–1.03)
0.123
460
(30.4)
497
(32.9)
Yusuf et al. Lancet 2003;362:777–81.

7. CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved - RESULTS continued -
Discontinuation because of adverse events
Placebo
Candesartan
Cause of discontinuation
(n=1509)
(n=1514) P
No.
(%)
No.
(%)
Hypotension
0.009 37
(2.4) 17
(1.1)
Increase in creatinine
0.0005 72
(4.8) 36
(2.4)
Hyperkalemia
0.029 22
(1.5) 9
(0.6)
Any adverse event or laboratory abnormality
0.001
270
(17.8)
204
(13.5)
Yusuf et al. Lancet 2003;362:777–81.

8. 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.