Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial - PubMed (original) (raw)

Clinical Trial

Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial

John J V McMurray et al. Lancet. 2003.

Abstract

Background: Angiotensin II type 1 receptor blockers have favourable effects on haemodynamic measurements, neurohumoral activity, and left-ventricular remodelling when added to angiotensin-converting-enzyme (ACE) inhibitors in patients with chronic heart failure (CHF). We aimed to find out whether these drugs improve clinical outcome.

Methods: Between March, 1999, and November, 1999, we enrolled 2548 patients with New York Heart Association functional class II-IV CHF and left-ventricular ejection fraction 40% or lower, and who were being treated with ACE inhibitors. We randomly assigned patients candesartan (n=1276, target dose 32 mg once daily) or placebo (n=1272). At baseline, 55% of patients were also treated with beta blockers and 17% with spironolactone. The primary outcome of the study was the composite of cardiovascular death or hospital admission for CHF. Analysis was done by intention to treat.

Findings: The median follow-up was 41 months. 483 (38%) patients in the candesartan group and 538 (42%) in the placebo group experienced the primary outcome (unadjusted hazard ratio 0.85 [95% CI 0.75-0.96], p=0.011; covariate adjusted p=0.010). Candesartan reduced each of the components of the primary outcome significantly, as well as the total number of hospital admissions for CHF. The benefits of candesartan were similar in all predefined subgroups, including patients receiving baseline beta blocker treatment.

Interpretation: The addition of candesartan to ACE inhibitor and other treatment leads to a further clinically important reduction in relevant cardiovascular events in patients with CHF and reduced left-ventricular ejection fraction.

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Comment in

Candesartan and heart failure: the allure of CHARM.
White HD. White HD. Lancet. 2003 Sep 6;362(9386):754-5. doi: 10.1016/S0140-6736(03)14294-8. Lancet. 2003. PMID: 13678864 No abstract available.
The CHARM programme.
Pechlaner C. Pechlaner C. Lancet. 2003 Nov 15;362(9396):1675-6; author reply 1678-9. doi: 10.1016/S0140-6736(03)14808-8. Lancet. 2003. PMID: 14630453 No abstract available.
The CHARM programme.
Jorde UP, Fox MT. Jorde UP, et al. Lancet. 2003 Nov 15;362(9396):1677; author reply 1678-9. doi: 10.1016/S0140-6736(03)14811-8. Lancet. 2003. PMID: 14630456 No abstract available.
Candesartan reduces cardiovascular death in CHF patients on ACE inhibitor.
Wiley G, Cole C. Wiley G, et al. J Fam Pract. 2004 Feb;53(2):93-4. J Fam Pract. 2004. PMID: 14764285 No abstract available.
Candesartan reduced mortality and hospital admissions in chronic heart failure.
Pitt B. Pitt B. ACP J Club. 2004 Mar-Apr;140(2):32-3. ACP J Club. 2004. PMID: 15122853 No abstract available.

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Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial - PubMed (original) (raw)