METHODS AND RESULTS: In COMET, 3029 patients with CHF were randomized to
carvedilol or
metoprolol tartrate and followed for a mean of 58 months. We analysed the prognostic relevance on other outcomes of
atrial fibrillation on the baseline electrocardiogram compared with no
atrial fibrillation and the impact of new onset
atrial fibrillation during follow-up. A multivariate analysis was performed using a Cox regression model where 10 baseline covariates were entered together with study treatment allocation. Six hundred patients (19.8%) had
atrial fibrillation at baseline. These patients were older (65 vs. 61 years), included more men (88 vs.78%), had more severe symptoms [higher New York Heart Association (NYHA) class] and a longer duration of
heart failure (all P<0.0001).
Atrial fibrillation was associated with significantly increased mortality [relative risk (RR) 1.29: 95% CI 1.12-1.48; P<0.0001], higher all-cause death or hospitalization (RR 1.25: CI 1.13-1.38), and cardiovascular death or hospitalization for worsening
heart failure (RR 1.34: CI 1.20-1.52), both P<0.0001. By multivariable analysis,
atrial fibrillation no longer independently predicted mortality. Beneficial effects on mortality by
carvedilol remained significant (RR 0.836: CI 0.74-0.94; P=0.0042). New onset
atrial fibrillation during follow-up (n=580) was associated with significant increased risk for subsequent death in a time-dependent analysis (RR 1.90: CI 1.54-2.35; P<0.0001) regardless of treatment allocation and changes in NYHA class.
CONCLUSION: In CHF,
atrial fibrillation significantly increases the risk for death and
heart failure hospitalization, but is not an independent risk factor for mortality after adjusting for other predictors of prognosis. Treatment with
carvedilol compared with
metoprolol offers additional benefits among patients with
atrial fibrillation. Onset of new
atrial fibrillation in patients on long-term beta-blocker
therapy is associated with significant increased subsequent risk of mortality and morbidity.