Association of digoxin with mortality in patients with advanced chronic kidney disease: A population-based cohort study

• Published in: PloS one 2021-01, Vol.16 (1), p.e0245620-e0245620
• Main Authors: Yang, Lii-Jia, Hsu, Shan-Min, Wu, Ping-Hsun, Lin, Ming-Yen, Huang, Teng-Hui, Lin, Yi-Ting, Kuo, Hung-Tien, Chiu, Yi-Wen, Hwang, Shang-Jyh, Tsai, Jer-Chia, Chen, Hung-Chun
• Format: Article
• Language: English
• Subjects: Acute coronary syndromes; Adenosine; Adenosine triphosphatase; Adverse events; Beta blockers; Biology and Life Sciences; Cardiovascular disease; Cardiovascular diseases; Catastrophic failure analysis; Chronic kidney failure; Clinical medicine; Clinical trials; Cohort analysis; Congestive heart failure; Dialysis; Digoxin; Drug therapy; Editing; Electronic mail; Enrollments; Enzymes; Epidermal growth factor receptors; Funding; Health insurance; Heart failure; Heart rate; Hemodialysis; Hemorrhage; Hospitalization; Hospitals; Hypertension; Internal medicine; Ischemia; Kidney diseases; Kidneys; Laboratories; Medical schools; Medicine; Medicine and Health Sciences; Meta-analysis; Methodology; Mortality; Muscle contraction; Nephrology; Patient outcomes; Patients; Pay for performance; Population; Population studies; Population-based studies; Potassium; Public health; Quality of life; Stroke; Triphosphatase
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0245620

Digoxin is commonly prescribed for heart failure and atrial fibrillation, but there is limited data on its safety in patients with chronic kidney disease (CKD). We conducted a population-based cohort study using the pre-end stage renal disease (ESRD) care program registry and the National Health Insurance Research Database in Taiwan. Of advanced CKD patient cohort (N = 31,933), we identified the digoxin user group (N = 400) matched with age and sex non-user group (N = 2,220). Multivariable Cox proportional hazards and sub-distribution hazards models were used to evaluate the association between digoxin use and the risk of death, cardiovascular events (acute coronary syndrome, ischemic stroke, or hemorrhagic stroke) and renal outcomes (ESRD, rapid decline in estimated glomerular filtration rate-eGFR, or acute kidney injury). Results showed that all-cause mortality was higher in the digoxin user group than in the non-user group, after adjusting for covariates (adjusted hazard ratio, aHR 1.63; 95% CI 1.23-2.17). The risk for acute coronary syndrome (sub-distribution hazard ratio, sHR 1.18; 95% CI 0.75-1.86), ischemic stroke (sHR 1.42; 95% CI 0.85-2.37), and rapid eGFR decline (sHR 1.00 95% CI 0.78-1.27) was not significantly different between two groups. In conclusion, our study demonstrated that digoxin use was associated with increased mortality, but not cardiovascular events or renal function decline in advanced CKD patients. This finding warns the safety of prescribing digoxin in this population. Future prospective studies are needed to overcome the limitations of cohort study design.