The angiotensin-receptor blocker candesartan significantly reduces hospitalization and death rates in patients with chronic heart failure, according to a major international clinical trial reported in the October 19th rapid access issue of Circulation.

The Candesartan in Heart Failure Assessment of Reduction in Morbidity and Mortality (CHARM) trial investigated whether the blocker could reduce all causes of death as well as cardiovascular morbidity and mortality in heart failure patients with a left ventricular ejection fraction of 40 percent or less (the threshold level for failure due to systolic dysfunction).

“The CHARM trials are the first definitive research effort to characterize the impact of adding an angiotensin-receptor blocker to standard treatment regimens in patients with a reduced ejection fraction,” said James B. Young, MD, the study’s lead author.

During a follow-up period of two to four years, all-cause death was 28 percent in people taking candesartan compared with 31 percent among people taking a placebo. Hospitalization rate was 28.1 percent for placebo patients and 22.5 percent for those taking candesartan.

This analysis of the CHARM low ejection fraction trials focused on 2,289 patients randomized to candesartan and 2,287 randomized to placebo at 618 sites in 26 countries, including the United States, Europe, and Australia (average age, 65 years; men, 74 percent). Average left ventricular ejection fraction was 29 percent.

All participants continued to receive standard therapies, including angiotensin-converting enzyme inhibitors, beta-blockers, and often an aldosterone antagonist.

Patients in the candesartan group initially received either 4 mg or 8 mg once daily, and with dose increased as tolerated to 32 mg once daily. They were followed for a median of 40 months.

Researchers found that the rate of cardiovascular death was 22.8 percent for candesartan patients compared with 26.2 percent for placebo patients. In addition, outcome data found that cardiovascular death or hospital admission for heart failure was observed in 41.3 percent of the placebo patients compared with 35.7 percent of candesartan patients. Researchers noted this significant effect occurred early and was maintained for the trial’s duration.

The CHARM research program as a whole, involving 7,601 CHF patients, is a “landmark trial,” Young said. He called it a “unique way to look at a complex treatment issue.” CHARM is one of the largest research efforts in heart failure.