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J Am Coll Cardiol, 2006; 47:1997-2004, doi:10.1016/j.jacc.2006.01.060 (Published online 24 April 2006).
© 2006 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: HEART FAILURE

Atrial Fibrillation and Risk of Clinical Events in Chronic Heart Failure With and Without Left Ventricular Systolic Dysfunction

Results From the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) Program

Lars G. Olsson, MB*, Karl Swedberg, MD, PhD, FACC*,1,*, Anique Ducharme, MD, MSc{dagger},5, Christopher B. Granger, MD, FACC{ddagger},2, Eric L. Michelson, MD, FACC§,4, John J.V. McMurray, MD, FACC||,1, Margareta Puu, PhD,4, Salim Yusuf, MD, DPhil, FACC#,3, Marc A. Pfeffer, MD, PhD, FACC**,1 on behalf of the CHARM Investigators

* Department of Medicine, Sahlgrenska University Hospital/Östra, Göteborg, Sweden
{dagger} Research Center, Montreal Heart Institute, Montreal, Quebec, Canada
{ddagger} Duke University Medical Center, Durham, North Carolina
§ AstraZeneca LP, Wilmington, Delaware
|| Department of Cardiology, Western Infirmary, Glasgow, Scotland
AstraZeneca, Mölndal, Sweden
# HGM-McMaster Clinic, Hamilton, Ontario, Canada
** Brigham and Women’s Hospital, Boston, Massachusetts.

Manuscript received September 26, 2005; revised manuscript received November 24, 2005, accepted January 2, 2006.

* Reprint requests and correspondence: Dr. Karl Swedberg, Sahlgrenska Academy, Department of Medicine, Sahlgrenska University Hospital/Östra, Göteborg, Sweden. (Email: karl.swedberg{at}hjl.gu.se).

OBJECTIVES: We assessed the risk of adverse cardiovascular (CV) outcomes associated with atrial fibrillation (AF) in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) program, which enrolled patients with chronic heart failure (CHF) and a broad range of ejection fractions (EFs).

BACKGROUND: Atrial fibrillation is associated with an increased risk of adverse CV outcomes in patients with CHF and reduced EF. The risk of AF in patients with CHF and preserved left ventricular ejection fraction (PEF) is unknown.

METHODS: A total of 7,599 patients with symptomatic CHF were randomized to candesartan or placebo. Patients were divided by baseline EF (≤40% or >40%) in low or preserved EF groups. Major outcomes were cardiovascular death or hospitalization for worsening heart failure, and all-cause mortality. Median follow-up was 37.7 months.

RESULTS: A total of 670 (17%) patients in the low EF group and 478 (19%) in the PEF group had AF at baseline. Atrial fibrillation predicted a high risk of cardiovascular morbidity and mortality regardless of baseline EF. Patients with AF and low EF had the highest absolute risk for adverse CV outcomes. However, AF was associated with greater relative increased risk of the major outcomes in patients with PEF than in patients with low EF: hazard ratio 1.72 (95% confidence interval [CI] 1.45 to 2.06) versus 1.29 (95% CI 1.14 to 1.46), respectively. The same was true for the risk of all-cause mortality. Candesartan was associated with similar treatment effects regardless of baseline rhythm.

CONCLUSIONS: Atrial fibrillation is associated with an increased risk of CV outcomes in patients with CHF and either reduced EF or PEF. Candesartan improved outcomes similarly regardless of baseline rhythm.

Abbreviations and Acronyms
  ACE-I = angiotensin-converting enzyme inhibitor
  AF = atrial fibrillation
  CHARM = Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity
  CHF = chronic heart failure
  COMET = Carvedilol Or Metoprolol European Trial
  CV = cardiovascular
  DIG = Digitalis Investigation Group
  ECG = electrocardiogram
  EF = ejection fraction
  HR = hazard ratio
  IN-CHF = Italian Network for Chronic Heart Failure
  LIFE = Losartan Intervention for End Point Reduction in Hypertension trial
  LVEF = left ventricular ejection fraction
  OR = odds ratio
  PEF = preserved left ventricular ejection fraction
  PRIME II = Second Prospective Ibopamine Evaluation trial
  SOLVD = Studies Of Left Ventricular Dysfunction
  Val-HeFT = Valsartan Heart Failure Trial




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