Digoxin Use to Control Ventricular Rate in Patients with Atrial Fibrillation and Heart Failure Is Not Associated with Increased Mortality

Abstract

Introduction. Digoxin is used to control ventricular rate in atrial fibrillation (AF). There is conflicting evidence regarding safety of digoxin. We aimed to evaluate the risk of mortality with digoxin use in patients with AF using meta-analyses. Methods. PubMed was searched for studies comparing outcomes of patients with AF taking digoxin versus no digoxin, with or without heart failure (HF). Studies were excluded if they reported only a point estimate of mortality, duplicated patient populations, and/or did not report adjusted hazard ratios (HR). The primary endpoint was all-cause mortality. Adjusted HRs were combined using generic inverse variance and log hazard ratios. A multivariate metaregression model was used to explore heterogeneity in studies. Results. Twelve studies with 321,944 patients were included in the meta-analysis. In all AF patients, irrespective of heart failure status, digoxin is associated with increased all-cause mortality (HR [1.23], 95% confidence interval [CI] 1.16-1.31). However, digoxin is not associated with increased mortality in patients with AF and HF (HR [1.08], 95% CI 0.99-1.18). In AF patients without HF digoxin is associated with increased all-cause mortality (HR [1.38], 95% CI 1.12-1.71). Conclusion. In patients with AF and HF, digoxin use is not associated with an increased risk of all-cause mortality when used for rate control.

Figure 1

Prisma flow diagram for study selection.

Figure 2

Funnel plot.

Figure 3

Forest plot showing combined effect of digoxin on all-cause mortality in studies with patients with atrial fibrillation only, atrial fibrillation with heart failure only, and atrial fibrillation with or without heart failure.

Figure 4

Effect of percentage of patients with CHF in individual studies on mortality risk of digoxin using a multivariate metaregression model; increased percentage of patients with CHF on the x-axis correlates with decreased HR on the y-axis.

Figure 5

Effect of percentage of hypertensive patients in individual studies on mortality risk of digoxin using a multivariate metaregression model including hypertension, heart failure, and previous stroke; increased percentage of patients with hypertension on the x-axis correlated with increased HR on the y-axis.