Clinical Question: Does candesartan effectively reduce mortality and prevent hospitalizations in patients with congestive heart failure (CHF) who have an ejection fraction less than 40 percent and are already taking an angiotensin-converting enzyme (ACE) inhibitor?

Setting: Outpatient (any)

Study Design: Randomized controlled trial (double-blinded)

Synopsis: In this part of the Cardiovascular Health and Risk Measurement trio of studies, patients who had New York Heart Association class II or worse CHF, who had an ejection fraction less than 40 percent, and who were already taking an optimal dosage of an ACE inhibitor were randomly assigned (masked allocation) to candesartan (n = 1,276) or placebo (n = 1,272). 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. In this study, the primary outcome of interest, assessed by intention-to-treat, was cardiovascular death or unplanned hospital admission for worsening CHF (although the real outcome of interest was all-cause mortality and hospitalization for any reason).

The researchers followed the patients for a median of 41 months. The number of deaths by any cause was similar in both groups (29.5 percent for candesartan, 32.4 percent for placebo). The number of patients requiring hospitalization for any reason did not differ significantly, but there was a small reduction in the total number of admissions (2,462 for candesartan versus 2,798 for placebo).

One interesting finding was that patients who also were taking beta blockers fared better on the primary end points. This would not have been anticipated based on subgroup analyses of other studies that suggested a harmful effect of combining beta blockers and angiotensin-receptor blockers.

Bottom Line: Patients with CHF who already take an ACE inhibitor and have an ejection fraction less than 40 percent have no significant difference in all-cause mortality if candesartan is added. Additionally, candesartan slightly reduces the average number of hospitalizations per patient. This study did not address quality of life. (Level of Evidence: 1b)