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.
OBJECTIVE
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 (< or =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.
Olsson
Lars G
LG
Department of Medicine, Sahlgrenska University Hospital/Ostra, Göteborg, Sweden.
Swedberg
Karl
K
Ducharme
Anique
A
Granger
Christopher B
CB
Michelson
Eric L
EL
McMurray
John J V
JJ
Puu
Margareta
M
Yusuf
Salim
S
Pfeffer
Marc A
MA
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy* / Q000401:mortality*; D001562:Benzimidazoles / Q000627:therapeutic use; D001713:Biphenyl Compounds; D002318:Cardiovascular Diseases / Q000401:mortality; D002908:Chronic Disease; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000401:mortality*; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012306:Risk; D013318:Stroke Volume; D013777:Tetrazoles / Q000627:therapeutic use; D018487:Ventricular Dysfunction, Left / Q000209:etiology
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan