Digoxin use is associated with pancreatic cancer risk but does not affect survival
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ORIGINAL PAPER
Digoxin use is associated with pancreatic cancer risk but does not affect survival Ben Boursi1,2,3,5,6 · Jared S. Huber2 · Kevin Haynes2 · Ronac Mamtani2,3,4 · Yu‑Xiao Yang1,2,3 Received: 4 April 2020 / Accepted: 3 October 2020 © Springer Nature Switzerland AG 2020
Abstract Purpose Digoxin affects several cellular pathways involved in tumorigenesis. We sought to determine the association between digoxin use and pancreatic cancer risk and survival. Methods A nested case–control study using The Health Improvement Network (THIN), a population-representative database from the United Kingdom (UK). Cases included all individuals with incident diagnosis of pancreatic cancer. Each case was matched to up to four controls using incidence density sampling based on age, sex, practice site, calendar time, and duration of follow-up. Exposure of interest was digoxin therapy before cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between digoxin use and pancreatic cancer risk were estimated using conditional logistic regression. We further conducted a retrospective cohort study among pancreatic cancer cases using Cox regression model in order to evaluate the association between digoxin use and overall survival. Results We identified 4,113 cases with incident pancreatic cancer and 16,072 matched controls. The adjusted OR for diagnosis of pancreatic cancer among active digoxin users was 1.41 (95% CI 1.16–1.72). The risk did not change among active users with duration of therapy of more than 1 year (adjusted OR of 1.39, 95% CI 1.11–1.76). Digoxin was not associated with change in overall survival with an adjusted hazard ratio of 0.97 (95% CI 0.81–1.18). Conclusions Digoxin use was associated with modestly increased pancreatic cancer risk but did not affect overall survival. Keywords Pancreatic cancer · Digoxin · Cancer survival
Introduction Ben Boursi and Jared S. Huber contributed equally to this manuscript. * Ben Boursi [email protected] 1
Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
2
Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
3
Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
4
Division of Hematology/Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
5
Tel-Aviv University, Tel‑Aviv, Israel
6
Department of Oncology, Sheba Medical Center, Tel‑Hashomer, Israel
Digoxin is a cardiac glycoside that has been used for centuries in the treatment of heart diseases. It inhibits the Na/K ATPase in cardiac myocytes, with an intended secondary effect of increased intracellular calcium and a positive inotropic effect [1]. Although there is a dearth of populationrepresentative estimates on the exact prevalence of digoxin users, the indications for digoxin us
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