Holt Anders, Strange Jarl Emanuel, Hansen Morten Lock, Lamberts Morten, Rasmussen Peter Vibe
Department of Cardiology, Herlev-Gentofte University Hospital, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Am J Med Open. 2025 Feb 13;13:100093. doi: 10.1016/j.ajmo.2025.100093. eCollection 2025 Jun.
Studies have reported excess risk of mortality associated with digoxin in atrial fibrillation (AF).This study sought to investigate if these findings could be replicated and whether a potential association could be explained by bias.
Using Danish Nationwide registers, a nested-case control study from 2012 to 2022 was conducted in a cohort of patients with AF. Cases were defined as death of any cause and the exposure was treatment with digoxin compared with beta blockers/verapamil. To investigate bias, additional analyses with negative control outcomes as case definitions-in which we would not expect a plausible association (eg, nursing home admission)-were employed. Associations were reported as hazard ratios (HRs) with 95% confidence intervals (95% CI).
A total of 59,748 cases were identified and matched 1:10 with controls (53% men, median age: 84 [IQR: 77-89]). Digoxin was associated with increased rates of mortality in the entire cohort (HR 1.85, 95% CI 1.78-1.92) as well as subgroups such as patients with heart failure (HR 1.84, 95% CI 1.65-2.06), diabetes (HR 1.85, 95% CI 1.6-2.14), and kidney disease (HR 1.37, 95% CI 1.04-1.8). Significant associations with all negative control outcomes were also found, most notably nursing home admissions (HR 1.79, 95% CI 1.67-1.93).
Digoxin use was associated with increased mortality in AF. However, negative control outcomes were also associated with digoxin use indicating that the described association between digoxin and mortality is likely not causal and being prescribed digoxin is merely a marker of more advanced disease and frailty.
研究报告称，地高辛与心房颤动（AF）患者的死亡风险增加有关。本研究旨在调查这些发现是否可以重复，以及潜在的关联是否可以用偏倚来解释。
利用丹麦全国登记系统，于2012年至2022年在一组房颤患者中进行了一项巢式病例对照研究。病例定义为任何原因导致的死亡，暴露因素为使用地高辛与使用β受体阻滞剂/维拉帕米进行比较。为了调查偏倚，采用了以阴性对照结局作为病例定义的额外分析，在这些阴性对照结局中，我们预计不会有合理的关联（例如，入住养老院）。关联以风险比（HR）及95%置信区间（95%CI）报告。
共识别出59748例病例，并与对照进行1:10匹配（53%为男性，中位年龄：84岁[四分位间距：77 - 89岁]）。地高辛与整个队列的死亡率增加相关（HR 1.85，95%CI 1.78 - 1.92），以及心力衰竭患者（HR 1.84，95%CI 1.65 - 2.06）、糖尿病患者（HR 1.85，95%CI 1.6 - 2.14）和肾病患者（HR 1.37，95%CI 1.04 - 1.8）等亚组的死亡率增加相关。还发现与所有阴性对照结局存在显著关联，最显著的是入住养老院（HR 1.79，95%CI 1.67 - 1.93）。
使用地高辛与房颤患者死亡率增加相关。然而，阴性对照结局也与地高辛使用相关，这表明所描述的地高辛与死亡率之间的关联可能不是因果关系，开具地高辛仅仅是疾病进展和虚弱程度更高的一个标志。
