Home > atrial fibrillation, Journal Club > Journal Club 5 December 2012

Journal Club 5 December 2012


Increased mortality among patients takingm digoxin-analysis from the AFFIRM study





Digoxin is frequently used for rate control of atrial fibrillation (AF). It has, however, been associated with increased
mortality. It remains unclear whether digoxin itself is responsible for the increased mortality (toxic drug effect) or
whether it is prescribed to sicker patients with inherently higher mortality due to comorbidities. The goal of our
study was to determine the relationship between digoxin and mortality in patients with AF.

Methods and results

The association between digoxin and mortality was assessed in patients enrolled in the AF Follow-Up Investigation of
Rhythm Management (AFFIRM) trial using multivariate Cox proportional hazards models. Analyses were conducted
in all patients and in subsets according to the presence or absence of heart failure (HF), as defined by a history of HF
and/or an ejection fraction ,40%. Digoxin was associated with an increase in all-cause mortality [estimated hazard
ratio (EHR) 1.41, 95% confidence interval (CI) 1.19–1.67, P , 0.001], cardiovascular mortality (EHR 1.35, 95% CI
1.06–1.71, P ¼ 0.016), and arrhythmic mortality (EHR 1.61, 95% CI 1.12–2.30, P ¼ 0.009). The all-cause mortality
was increased with digoxin in patients without or with HF (EHR 1.37, 95% CI 1.05–1.79, P ¼ 0.019 and EHR
1.41, 95% CI 1.09–1.84, P ¼ 0.010, respectively). There was no significant digoxin–gender interaction for all-cause
(P ¼ 0.70) or cardiovascular (P ¼ 0.95) mortality.


Digoxin was associated with a significant increase in all-cause mortality in patients with AF after correcting for clinical
characteristics and comorbidities, regardless of gender or of the presence or absence of HF. These findings call into
question the widespread use of digoxin in patients with AF.

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