my personal edition > congestive heart failure > news


  E-Mail this DGDispatch to a colleague

DGDispatch

CHARM Trials Demonstrate Add-On Benefit of Candesartan for Heart Failure: Presented at ESC(CARD)

By Peggy Peck

VIENNA, AUSTRIA -- September 3, 2003 -- Candesartan was associated with a 12% reduction in risk of cardiovascular death and a 16% relative reduction in the combined end point of cardiovascular death or congestive heart failure (CHF) hospitalization in a series of related studies.

The results from the series of studies, all under the name Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM), were presented here on August 31^st at the European Society of Cardiology (ESC) Congress 2003.

Marc Pfeffer, MD, professor of medicine, Harvard Medical School, and senior physician, Brigham and Women's Hospital, Boston, Massachusetts, said at an ESC press conference that the CHARM trials are the largest trial of patients with symptomatic heart failure and the first trials to assess the efficacy of an angiotensin receptor blocker (ARB) in combination with an ACE inhibitor.

The ARB-ACE combination was assessed in the CHARM-added trial that enrolled 2,548 patients with ejection fraction (EF) of 40% or less. In that trial, patients were randomized to candesartan or placebo plus an ACE inhibitor.

In the CHARM-alternative trial, 2,028 patients who were ACE-inhibitor intolerant were randomized to candesartan or placebo. In the CHARM preserved trial, 3,025 patients with or without an ACE inhibitor were randomized to candesartan or placebo.

In all study arms, candesartan was given "on top of standard therapy that included beta blockers, diuretics, digoxin, spironolactone and calcium antagonists," said Karl Swedberg, MD, professor of medicine, Göteborg University and Sahlgrenska University Hospital/Ostra, Göteborg, Sweden. Dr. Swedberg co-chaired the multinational study with Dr. Pfeffer.

In each study arm, candesartan was initiated at 4-8 mg and titrated up to a target dose of 32 mg.

Patients were followed every 4 months after titration for a minimum follow-up of 2 years.

In the CHARM alternative trial, candesartan was associated with a 23% reduction in risk of cardiovascular death or CHF admissions, while in CHARM-added trial the reduction in the combined end point was 15%, said Dr. Pfeffer.

In the CHARM-preserved trial there was no difference in the rate of cardiovascular deaths but fewer candesartan patients (402) were hospitalized for CHF than placebo patients (566), although this difference did not reach statistical significance, Dr. Pfeffer said.

Sidney Smith, Jr., MD, professor of medicine, University of North Carolina, Chapel Hill, said in an interview that the CHARM results are likely to have the greatest clinical influence for treatment of patients who cannot tolerate an ACE inhibitor. "At least for those patients, the study benefits are clear."

He said the choice is not as clear when treating patients who can tolerate ACE-inhibitors. In such cases, the treatment decision "requires a bit more thought," said Dr. Smith, who was not involved in the study. Candesartan might offer the greatest benefit to patients with systolic dysfunction on an ACE.

In addition to the presentation at the ESC conference, results of the CHARM studies were published Monday in The Lancet online.


[Study title: Candesartan in heart failure: effects on mortality and morbidity. Abstract 82]

E-Mail this DGDispatch to a colleague

To print, use this version