Effect of digoxin on all-cause and cardiovascular mortality in patients with atrial fibrillation with and without heart failure: an umbrella review of systematic reviews and 12 meta-analyses
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Published:2023-03-06
Issue:4
Volume:79
Page:473-483
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ISSN:0031-6970
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Container-title:European Journal of Clinical Pharmacology
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language:en
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Short-container-title:Eur J Clin Pharmacol
Author:
Gazzaniga GianlucaORCID, Menichelli DaniloORCID, Scaglione Francesco, Farcomeni AlessioORCID, Pani AriannaORCID, Pastori DanieleORCID
Abstract
Abstract
Purpose
To perform a systematic umbrella review with meta-analysis to evaluate the certainty of evidence on mortality risk associated with digoxin use in patients with atrial fibrillation (AF) with or without heart failure (HF).
Methods
We systematically searched MEDLINE, Embase, and Web of Science databases from inception to 19 October 2021. We included systematic reviews and meta-analyses of observational studies investigating digoxin effects on mortality of adult patients with AF and/or HF. The primary outcome was all-cause mortality; secondary outcome was cardiovascular mortality. Certainty of evidence was evaluated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool and the quality of systematic reviews/meta-analyses by the A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR2) tool.
Results
Eleven studies accounting for 12 meta-analyses were included with a total of 4,586,515 patients. AMSTAR2 analysis showed a high quality in 1, moderate in 5, low in 2, and critically low in 3 studies. Digoxin was associated with an increased all-cause mortality (hazard ratio [HR] 1.19, 95% confidence interval [95%CI] 1.14–1.25) with moderate certainty of evidence and with an increased cardiovascular mortality (HR 1.19, 95%CI 1.06–1.33) with moderate certainty of evidence. Subgroup analysis showed that digoxin was associated with all-cause mortality both in patients with AF alone (HR 1.23, 95%CI 1.19–1.28) and in those with AF and HF (HR 1.14, 95%CI 1.12–1.16).
Conclusion
Data from this umbrella review suggests that digoxin use is associated with a moderate increased risk of all-cause and cardiovascular mortality in AF patients regardless of the presence of HF.
Trial registration
This review was registered in PROSPERO (CRD42022325321).
Funder
Università degli Studi di Roma La Sapienza
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Pharmacology,General Medicine
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