Highlights
- •In 2015, 3 independent meta-analyses raised concerns about digoxin therapy being associated with an increased mortality risk in patients with atrial fibrillation and with heart failure. This updated systematic review and meta-analysis including the most recent publications confirms in more than 810,000 patients that digoxin use is associated with increased mortality in such patients. In incident digoxin users, an even higher risk for all-cause mortality was demonstrated. Our results call for randomized studies and for a thorough reappraisal of this topic in future guideline recommendations.
In 2015, 3 independent meta-analyses raised concerns about digoxin therapy being associated
with an increased mortality risk in patients with atrial fibrillation (AF) and with
heart failure (HF). Although several other studies have been published since then
fostering these safety issues, the most recent 2016 European guidelines for AF still
recommend this therapy as a class I indication. We performed an updated systematic
review and random-effect meta-analysis on publications up to March 2018 reporting
data on digoxin associated mortality in subjects with AF or HF. Based on the adjusted
survival data of all identified 37 trials comprising a total of 825,061 patients,
digoxin use was associated with an increased relative risk of all-cause mortality
(hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.05 to 1.29, p <0.01). Treatment
with digoxin was associated with an increased mortality risk in the subgroup of patients
with AF (n = 627,620, HR 1.23, 95% CI, 1.17 to 1.30, p <0.01), and in the subgroup
of patients with HF (n = 197,441, HR 1.11, 95% CI, 1.06 to 1.16, p<0.01). A sensitivity
analysis of studies reporting data on new digoxin users (n = 41,687) demonstrated
an even higher risk for all-cause mortality compared with patients not receiving cardiac
glycosides (HR 1.47, 95% CI, 1.15 to 1.88, p <0.01). In conclusion, this updated meta-analysis
confirms that digoxin use is associated with increased mortality in patients with
AF or HF.
Graphical Abstract
Graphical Abstract
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Article info
Publication history
Published online: October 03, 2018
Accepted:
September 27,
2018
Received in revised form:
September 26,
2018
Received:
July 11,
2018
Identification
Copyright
© 2018 Elsevier Inc. All rights reserved.
