Candesartan reduces cardiovascular death in CHF patients on ACE inhibitor

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Candesartan reduces cardiovascular death in CHF patients on ACE inhibitor

J Fam Pract. 2004 February;53(2):93-105

By

Ginger Wiley, MD

Charles Cole, MD

BACKGROUND: Despite high doses of an ACE inhibitor, some angiotensin II is still produced by the kidney. ARB treatment, in addition to an ACE inhibitor, might offer a benefit. The addition of valsartan to an ACE inhibitor in a previous study decreased cardiovascular mortality but did not affect overall mortality. A recent study combining valsartan and captopril (Capoten) for patients with a recent myocardial infarction and heart failure showed increased adverse events without any change in survival compared with captopril or valsartan alone.¹ This study evaluated the addition of the ARB candesartan to patients with heart failure already receiving an ACE inhibitor.
POPULATION STUDIED: The investigators enrolled patients aged 18 years or older with left ventricular ejection fraction of 40% or lower and New York Heart Association functional class II–IV CHF who were on optimal, stable doses of ACE inhibitors. Other variables, such as age, race, comorbidities, and medications were similar to typical family practice patients with CHF.
STUDY DESIGN AND VALIDITY: Of the 2548 subjects enrolled, 1276 were assigned to receive candesartan and 1272 to receive placebo. Starting doses were 4 to 8 mg once daily, and the dose was doubled every 2 weeks as tolerated until a target dose of 32 mg was reached. Patients were seen at 2 weeks, 4 weeks, 6 weeks, 6 months, and then every 4 months until the end of the trial. The median follow-up was 41 months. The study was well done. Randomization was computer-generated, both subjects and investigators were blinded to treatment assignment, and allocation was concealed. The analysis was intention-to-treat and included all randomized patients. The patient population was mostly male (79%) and of European decent (90%). The randomization scheme ended up placing more smokers in the placebo group (18.5% vs 15.2%), which could have increased the cardiovascular mortality in this group. Almost all (99.8%) patients were followed completely through the study, with only 4 patients lost to follow-up. (Level of evidence:1b)
OUTCOMES MEASURED: The primary outcome was cardiovascular death or unplanned admission to the hospital for worsening CHF. All-cause mortality and the numbers of hospitalizations for any reason were also measured.
RESULTS: Overall, 483 (37.9%) patients in the candesartan group and 538 (42.3%) in the placebo group experienced the primary outcome of cardiovascular death or unplanned admission to the hospital for worsening CHF (P=.011; number needed to treat [NNT]=23 for 41 months).

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Candesartan reduces cardiovascular death in CHF patients on ACE inhibitor

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