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

Oxfordjournals: 11/27/12

Aims 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 = 0.016), and arrhythmic mortality (EHR 1.61, 95% CI 1.12–2.30, P = 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 = 0.019 and EHR 1.41, 95% CI 1.09–1.84, P = 0.010, respectively). There was no significant digoxin–gender interaction for all-cause (P = 0.70) or cardiovascular (P = 0.95) mortality. Read more