Author + information
- Received September 26, 2005
- Revision received November 24, 2005
- Accepted January 2, 2006
- Published online May 16, 2006.
- Lars G. Olsson, MB⁎,
- Karl Swedberg, MD, PhD, FACC⁎,1,⁎ (, )
- Anique Ducharme, MD, MSc†,5,
- Christopher B. Granger, MD, FACC‡,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,
- CHARM Investigators
- ↵⁎Reprint requests and correspondence:
Dr. Karl Swedberg, Sahlgrenska Academy, Department of Medicine, Sahlgrenska University Hospital/Östra, Göteborg, Sweden.
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.
↵1 Drs. McMurray, Pfeffer, and Swedberg have received research grants or other research support from, served on the speakers’ bureau of, received honoraria from, and consulted for AstraZeneca.
↵2 Dr. Granger has received a research grant from and served as a consultant to AstraZeneca.
↵3 Dr. Yusuf has received research grants from, served on the speakers’ bureau of and/or received honoraria from, and served as a consultant to AstraZeneca.
↵4 Drs. Michelson and Puu are employees of AstraZeneca.
↵5 Dr. Ducharme is supported by the Fonds de Recherche en Santé du Québec.
The CHARM program was funded by AstraZeneca, which was responsible for data collection and analysis. The Executive Committee academic leadership, consisting of Drs. Swedberg, Granger, McMurray, Yusuf, and Pfeffer, supervised the management of the study and were primarily responsible for the interpretation of the data, preparation, review, and approval of the manuscript.
- Received September 26, 2005.
- Revision received November 24, 2005.
- Accepted January 2, 2006.
- American College of Cardiology Foundation