Prognostic relevance of atrial fibrillation in patients with chronic heart failure on long-term treatment with beta-blockers: results from COMET

Abstract

Aims: Atrial fibrillation is common in patients with chronic heart failure (CHF). We analysed the risk associated with atrial fibrillation in a large cohort of patients with chronic heart failure all treated with a beta-blocker.

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.