Department of Pharmacy Practice, University of Connecticut School of Pharmacy, University of Connecticut, Storrs, Connecticut, USA.
Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, USA.
Pharmacotherapy. 2021 Apr;41(4):394-404. doi: 10.1002/phar.2510. Epub 2021 Feb 24.
Once a routine part of atrial fibrillation (AF) management, digoxin use has declined. Likely hastening this decline are findings from several studies and systematic reviews identifying a potential association between digoxin use and all-cause mortality in AF populations. However, inconsistency exists within some of these studies potentially leading to confusion among clinicians. To critically evaluate the current literature to contextualize the associations between digoxin and mortality risk in patients with AF by performing an overview of systematic reviews. We searched MEDLINE, Cochrane Central Database of Systematic Reviews, and SCOPUS from their earliest date through October 12, 2020, to identify systematic reviews (SRs) that included studies enrolling patients with AF or atrial flutter and evaluated the association between digoxin use and all-cause mortality. We used the AMSTAR 2 tool to assess the risk of bias for each included SR. Results from reviews are qualitatively synthesized. Our search identified 10 SRs that met our inclusion criteria. Of the 41 unique AF studies included in these SRs, 41% were cohort studies, 29% were post hoc analyses of randomized controlled trials (RCTs), 15% were RCTs, and 15% were registry studies. Based on our AMSTAR 2 assessment, the overall confidence in the results of the 10 reviews was rated as "moderate" in three SRs, "low" in three SRs, and "critically low" in the rest. Except for one review, each included SR shows that digoxin use in AF is associated with a 15 to 38% higher risk of all-cause mortality. This association may be greater when AF-only populations are considered compared with a mix of AF and heart failure populations. Serum digoxin concentration (SDC) data were infrequently considered, but available data suggested a greater association between increasing SDC and all-cause mortality. This overview of reviews found general consistency regarding the association between digoxin use and higher all-cause mortality in AF populations. However, heterogeneity exists among and between SRs and an unmet need exists for additional study in a RCT setting with close monitoring and reporting of SDC to better inform clinical practice.
地高辛曾经是心房颤动 (AF) 管理的常规部分，但现在已不常使用。可能促使这种下降的原因是，几项研究和系统评价发现，地高辛的使用与 AF 人群的全因死亡率之间存在潜在关联。然而，这些研究中的一些结果并不一致，这可能导致临床医生感到困惑。为了通过对系统评价进行概述来批判性地评估当前文献，以确定 AF 患者地高辛与死亡率风险之间的关联，我们检索了 MEDLINE、Cochrane 系统评价数据库和 SCOPUS，从最早日期到 2020 年 10 月 12 日，以确定包括 AF 或心房扑动患者并评估地高辛使用与全因死亡率之间关联的系统评价。我们使用 AMSTAR 2 工具评估每个纳入的 SR 的偏倚风险。综述结果进行定性综合。我们的搜索确定了 10 项符合纳入标准的 SR。在这些 SR 中包含的 41 项独特的 AF 研究中，41%为队列研究，29%为随机对照试验 (RCT) 的事后分析，15%为 RCT，15%为登记研究。根据我们的 AMSTAR 2 评估，10 项综述的结果总体置信度在三项 SR 中评为“中度”，在三项 SR 中评为“低度”，在其余 SR 中评为“极低度”。除了一项综述外，每一项纳入的 SR 都表明，AF 中地高辛的使用与全因死亡率增加 15%至 38%相关。当仅考虑 AF 人群时，与 AF 和心力衰竭混合人群相比，这种关联可能更大。很少考虑地高辛血清浓度 (SDC) 数据，但现有数据表明，SDC 与全因死亡率之间的关联更大。这项综述发现，在 AF 人群中地高辛的使用与更高的全因死亡率之间存在一般一致性。然而，SR 之间以及 SR 内部存在异质性，并且在 RCT 环境中需要进一步研究，密切监测和报告 SDC，以更好地为临床实践提供信息。
