Department of Medical Biotechnology and Translational Medicine, Postgraduate School of Clinical Pharmacology and Toxicology, Università degli Studi di Milano, 20122, Milan, Italy.
Department of General and Specialized Surgery "Paride Stefanini", Sapienza University of Rome, 00185, Rome, Italy.
Eur J Clin Pharmacol. 2023 Apr;79(4):473-483. doi: 10.1007/s00228-023-03470-y. Epub 2023 Mar 6.
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).
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.
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).
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.
This review was registered in PROSPERO (CRD42022325321).
系统地进行伞式综述和荟萃分析，以评估地高辛在伴有或不伴有心力衰竭（HF）的心房颤动（AF）患者中的死亡率风险的证据确定性。
我们系统地检索了 MEDLINE、Embase 和 Web of Science 数据库，检索时间从建库到 2021 年 10 月 19 日。我们纳入了观察性研究的系统评价和荟萃分析，这些研究调查了地高辛对 AF 和/或 HF 成年患者死亡率的影响。主要结局是全因死亡率；次要结局是心血管死亡率。证据确定性通过推荐评估、制定与评估（GRADE）工具进行评估，系统评价/荟萃分析的质量通过评估系统评价的测量工具 2（AMSTAR2）工具进行评估。
纳入了 11 项研究，共计 12 项荟萃分析，涉及 4586515 名患者。AMSTAR2 分析显示，有 1 项研究质量为高，5 项为中，2 项为低，3 项为极低。地高辛与全因死亡率增加相关（风险比[HR] 1.19，95%置信区间[95%CI] 1.14-1.25），证据确定性为中，与心血管死亡率增加相关（HR 1.19，95%CI 1.06-1.33），证据确定性为中。亚组分析显示，地高辛与单独 AF 患者（HR 1.23，95%CI 1.19-1.28）和 AF 合并 HF 患者（HR 1.14，95%CI 1.12-1.16）的全因死亡率均相关。
本伞式综述的数据表明，地高辛的使用与 AF 患者的全因和心血管死亡率的中度增加风险相关，无论 HF 是否存在。
本综述在 PROSPERO（CRD42022325321）中进行了注册。
