Clinical Question: Does candesartan effectively reduce mortality and prevent hospitalizations in patients with congestive heart failure (CHF)?
Setting: Outpatient (any)
Study Design: Randomized controlled trial (double-blinded)
Synopsis: Patients with CHF are hospitalized frequently and, despite treatment advances, have high mortality rates. Pfeffer and colleagues point out that randomized trials have shown the lifesaving and symptomatic benefits of using angiotensin-converting enzyme (ACE) inhibitors, beta blockers, and spironolactone in patients with CHF. The Cardiovascular Health and Risk Measurement studies compared an angiotensin-receptor blocker, candesartan, with placebo in men and women with New York Heart Association class II or worse CHF. The authors summarized the results of three separate trials on the following specific risk/severity groups of patients with CHF: (1) ejection fraction greater than 40 percent; (2) ejection fraction less than 40 percent, but taking an ACE inhibitor; and (3) ejection fraction less than 40 percent, but not taking an ACE inhibitor because of intolerance.
Patients were randomly assigned (masked allocation) to receive treatment with candesartan (n = 3,803) or placebo (n = 3,796). The initial dosage, chosen by the study physician, was 4 mg or 8 mg of candesartan once daily or matching placebo. The dosage was doubled every two weeks to a target dosage of 32 mg once daily, if tolerated. Once the patients reached their target dosage, the investigators followed up every four months. Patients were to be followed for at least two years (the actual median follow-up was 38 months). The study protocol allowed for co-interventions such as beta blockers, spironolactone, and ACE inhibitors.
The many outcomes assessed by intention-to-treat included all-cause mortality, cardiac mortality, cardiac-related hospital admissions (but not total admissions), and various pooled combinations of outcomes. Although the authors analyzed the pre-specified subgroups appropriately, it is not apparent whether they adjusted for the number of outcomes assessed. Complete follow-up was obtained for 99.9 percent of the patients in the study.
By the end of the study, 23.2 percent of patients in the candesartan group had died, compared with 24.8 percent in the placebo group (number needed to treat [NNT] = 62 for three years). The annual mortality rate per 100 years of follow-up was 8.1 and 8.8 percent, respectively (NNT = 143 per year). In the candesartan group, 2,374 patients had 6,690 hospital admissions for any reason, compared with 2,423 patients in the placebo group who had 7,178 admissions (P = .2 for patients; P = .015 for admissions). The authors also reported reductions in rates of mortality and hospital admission attributed to specific conditions, but these are subject to various biases and are less relevant to the all-cause outcomes.
Bottom Line: Candesartan is marginally better than placebo in the treatment of CHF. Treating 142 patients with candesartan for one year would prevent one death from any cause. Candesartan slightly reduces the average number of hospitalizations for CHF per patient. The study did not compare candesartan with other effective treatments for CHF. (Level of Evidence: 1b)