Digoxin-induced anemia among patients with atrial fibrillation and heart failure: clinical data analysis and drug-gene interaction network

// Yubi Lin 1, 2 , Siqi He 1, 2 , Ruiling Feng 1, 2 , Zhe Xu 3 , Wanqun Chen 4 , Zifeng Huang 1, 2 ,Yang Liu 1 , Qianhuan Zhang 1 , Bin Zhang 1 , Kejian Wang 5 and Shulin Wu 1 1 Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences and Medical School of South China University of Technology, Guangzhou 510080, P.R. China 2 The First Affiliated Hospital of Jinan University, Guangzhou 510630, P.R. China 3 Division of Cardiac Surgery, First Affiliated Hospital of Sun-Yat-sen University, Guangzhou 510080, P.R. China 4 Department of Biochemistry and Molecular Biology, Medical College, Jinan University, Guangzhou 510632, P.R. China 5 Lin He’s Academician Workstation of New Medicine and Clinical Translation at The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, P.R. China Correspondence to: Kejian Wang, email: kejian.wang@gzhmu.edu.cn Shulin Wu, email: doctorwushulin@163.com Keywords: digoxin, atrial fibrillation, heart failure, anemia, FDA adverse event reporting system Received: March 13, 2017     Accepted: April 25, 2017     Published: June 16, 2017 ABSTRACT Digoxin is widely used to treat various heart conditions. In order to clarify the association between digoxin and anemia adverse reaction, we inspected case reports submitted to the FDA Adverse Event Reporting System (FAERS) between January 2004 and December 2015. These reports involved 75618 atrial fibrillation patients and 15699 heart failure patients. Compared to other therapies, digoxin treatment was significantly more likely to be concurrent with anemia adverse reaction among both atrial fibrillation patients (pooled OR = 1.38, 95% CI 1.14–1.68, P-value = 0.001) and heart failure patients (pooled OR =1.50, 95% CI 1.33–1.59–, P =4.27×10 -5 ). We further explored previously published evidences and found 821 human genes directly or indirectly interacting with digoxin. Functional analysis indicated that these genes were significantly enriched in the biological processes of iron transport, which are closely related to iron deficiency anemia. Taken together, our retrospective analysis demonstrated the significant association between digoxin treatment and anemia adverse reaction, which should be seriously considered in clinical practice. Functional enrichment analysis on digoxin-related genes warranted subsequent research on the underlying toxicological mechanisms.