Should clinicians consider avoiding digoxin in patients with AF?

Abstract

Use of digoxin in patients with atrial fibrillation (AF) was associated with an increased risk of death—specifically when serum concentrations were 1.2 ng/mL or higher or when treatment was newly initiated, according to results of a new analysis published in the Journal of the American College of Cardiology.1J Am Coll Cardiol. 2018; 71: 1063-1074Crossref PubMed Scopus (85) Google Scholar These results are concerning because current practice guidelines recommend use of digoxin for rate control in patients with AF, particularly those with heart failure. Therefore, clinicians must now take this new data into consideration and determine if digoxin is an optimal choice for this patient population. Lopes and colleagues conducted an analysis of data from patients enrolled in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial to determine the association between digoxin use and death. The researchers performed a post-hoc digoxin subgroup analysis of data from 17,897 patients, with 5,824 patients receiving digoxin and 12,073 not on this therapy at baseline, to determine the time to all-cause mortality, cardiovascular and noncardiovascular mortality, and sudden cardiac death. A propensity score–adjusted analysis was used to assess the association between digoxin use and mortality, and for new digoxin users during the trial versus propensity-matched control patients. In addition, patients with heart failure were assessed as a subgroup (n = 6,693), as was the effect of serum digoxin concentrations on outcomes. The researchers reported that baseline digoxin use was not associated with an increased risk of all-cause mortality, cardiovascular mortality, noncardiovascular-related death, sudden cardiac death, or heart failure hospitalization, although the rates of these events were all numerically higher in the digoxin group compared with no baseline digoxin use. No significant differences were observed in patients who had or did not have heart failure. In the 4,434 patients in which baseline serum digoxin concentrations were measured at baseline, patients with digoxin levels of 1.2 ng/mL or more did have a significant increase in the risk of death (adjusted hazard ratio 1.56 [95% CI 1.20–2.04]). They noted that after adjustment for potential confounders, baseline serum digoxin concentrations as a continuous variable exhibited a direct relationship with overall mortality. Specifically, for every 0.5 ng/mL increase in baseline serum digoxin concentrations, an increase in the risk of death was observed in the overall population. This was seen in patients with and without heart failure. Finally, for the analysis of new digoxin users in the trial compared with matched controls, the new users had a significantly higher total mortality (adjusted hazard ratio 1.78 [95% CI 1.37–2.31]). Again, these results were consistent, regardless of whether the patients had heart failure. Digoxin has been used for many years in patients with cardiac conditions, given its availability since the 1930s. The researchers pointed out that approximately one-third of patients with AF worldwide are treated with digoxin, and the 2016 AF guidelines continue to give digoxin a Class I recommendation for patients with a reduced or preserved left ventricular ejection fraction. The authors concluded, “In the absence of randomized trial data showing its efficacy and safety, digoxin should be used with caution and with monitoring of its serum concentration in patients with AF, and should preferably be avoided if symptoms can be alleviated with other treatments.” In an accompanying editorial, the author summarized digoxin’s long history and commented on the current results and potential confounders to the analysis.2J Am Coll Cardiol. 2018; 71: 1075-1077Crossref PubMed Scopus (3) Google Scholar Despite potential limitations, he wrote, “for the majority of patients with AF, there is no reason to believe that there is any benefit but rather possible or probable harm of digoxin compared with other atrioventricular nodal agents.”