| Authors |
| Yusuf S, Pfeffer MA, Swedberg K, et al. |
| Title |
| Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved trial |
| References |
| Lancet 2003;362:777-81 |
| Background |
| Trials designed specifically for patients with CHF and preserved LVEF (>40%) are few and pharmacologic treatment is frequently extrapolated from the literature for HF patients with low LVEF. |
| Purpose |
| To determine whether the ARB, candesartan, improves survival rates and clinical outcomes in chronic heart failure patients with preserved left ventricular ejection fraction (>40%). |
| Design |
- Randomized, double-blind, placebo-controlled trial
- 3023 patients, age ≥18 years with NYHA class II-IV symptoms, history of cardiac hospitalization and LVEF >40%
- diuretics, digoxin, beta-blockers and spironolactone use permitted; ACE inhibitors eventually allowed in appropriate patients after publication of HOPE
|
| Exclusion Criteria |
- serum creatinine ≥265 µmol/L, serum potassium ≥5.5 mmol/L
- Symptomatic hypotension, known bilateral renal artery stenosis
- critical mitral or aortic stenosis; recent MI, CVA or CABG
- ARB therapy in the previous 2 weeks
|
| Follow-Up |
| Median of 36.6 months |
| Treatment Regimen |
- candesartan 4 mg or 8 mg once daily, dose doubled every 2 weeks to target of 32 mg once daily (as tolerated by patient) vs. placebo
- blood pressure, potassium and creatinine monitoring with each titration and follow-up at week 2, 4, 6, month 6 and then every 4 mos.
|
| Results |
Primary Endpoints Death from cardiovascular causes or hospitalization for worsening heart failure: 22% (candesartan) vs. 24% (placebo); unadjusted hazard ratio 0.89 (0.77-1.03), p=0.118. - Of note, the total number of HF hospitalizations was significantly different [402 (candesartan) vs. 566 (placebo), p=0.014], as well as the need for at least one HF hospitalization [230 (candesartan) vs. 279 (placebo), p=0.017] between the two groups.
Secondary Endpoints Cande-
sartan
n=1514 | Placebo
n=1509 | Hazard Ratio | p |
|---|
| CV death, HF hospitalization, MI |
|---|
| 24.1% | 26.4% | 0.90 (0.78-1.03) | 0.126 | | CV death, HF hospitalization, MI, stroke |
|---|
| 25.6% | 28.4% | 0.88 (0.77-1.01) | 0.078 | | CV death, HF hospitalization, MI, stroke, coronary revascularization |
|---|
| 30.4% | 32.9% | 0.91 (0.80-1.03) | 0.123 | - Rates of candesartan discontinuation higher than in placebo for hypotension (p=0.009), creatinine increase (p=0.0005), hyperkalemia (p=0.029)
- New-onset diabetes lower in candesartan vs. placebo group (47 vs. 77, HR 0.60 [0.41-0.86], p=0.005)
|
| Summary |
| Candesartan therapy in HF patients with preserved LVEF did not reduce the primary composite endpoint of CV death or HF hospitalization. However, the risk for HF hospitalization was lower in the candesartan group as compared to placebo. |