Analyzing gender and racial effects of digoxin vs diltiazem in atrial fibrillation mortality using large EHR data

  • Shrie Raam Sathyanarayanan M.S. Center for Health Systems Innovation (CHSI)
  • Michael Sutton D.O. Oklahoma State University College of Osteopathic Medicine
  • William Paiva PhD. Center for Health Systems Innovation (CHSI)
Keywords: Atrial fibrillation mortality, digoxin vs diltiazem, Atrial fibrillation EHR data, gender and racial effects in atrial fibrillation, digoxin moratlity, digoxin and diltiazem in atrial fibrillation, digitalis in atrial fibrillation


Digoxin is an atrial fibrillation (AF) rate control drug that is still in use. New randomized trial data comparing digoxin with other agents is unlikely to become available, but observational data exists in the form of large patient databases. We compared the mortality rates between Digoxin and Diltiazem using the Cerner Healthfacts Data. The study was performed on data with 52,775 U.S. patients with atrial fibrillation. The goal of the study was to assess the mortality versus survival rates between patients. Patients’ characteristics were reviewed among those receiving either a calcium channel antagonist (diltiazem) or digoxin. The mortality rates for patients who took digoxin were greater than that of patients who took diltiazem and had 1.31 times the risk of mortality [5.23% vs 3.98%, RR 1.31, CI 1.21-1.42, p < 0.001]. African Americans had the highest mortality rate compared to other races [6.28%, p<0.0001]. The age (in years) of patients treated with digoxin was higher than that of patients treated with diltiazem [74.96 vs 68.45, p<0.0001]. Length of stay (in days) of patients with digoxin was also significantly higher than that of diltiazem patients [74.96 vs 68.45, p<0.0001; 5.95 vs 4.99, p<0.0001]. Within certain races, digoxin mortality rates were higher between male and female patients. The mortality rate differences show adverse outcomes and increased risk of mortality was found in patients taking digoxin.


Withering W. An account of the foxglove and some of its medical uses, with practical remarks on dropsy, and other diseases. In Willins FA, Keys TE, eds. Classics of Cardiology. Volume I. New York, NY: Henry Schuman, Dover Publications; 1941: 231–252

Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. New England Journal of Medicine. 1997 Feb 20;336 (8):525-33

Digitalis in Acute Atrial Fibrillation (DAAF) Trial Group. Intravenous digoxin in acute atrial fibrillation: results of a randomized, placebo-controlled multicentre trial in 239 patients. European Heart Journal. 1997 Apr 1;18(4):649-54

Anderson J., et. al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. Circulation. 2014; 129

Fauchier L, Grimard C, Pierre B, Nonin E, Gorin L, Rauzy B, Cosnay P, Babuty D, Charbonnier B. Comparison of beta blocker and digoxin alone and in combination for management of patients with atrial fibrillation and heart failure. The American journal of cardiology. 2009 Jan 15;103(2):248-54

Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. New England Journal of Medicine. 1997 Feb 20;336(8):525-33

Olshansky B, Rosenfeld LE, Warner AL, Solomon AJ, O'Neill G, Sharma A, Platia E, Feld GK, Akiyama T, Brodsky MA, Greene HL. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study: approaches to control rate in atrial fibrillation. Journal of the American College of Cardiology. 2004 Apr 7;43(7):1201-8

Ziff OJ, Lane DA, Samra M, Griffith M, Kirchhof P, Lip GY, Steeds RP, Townend J, Kotecha D. Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data. Bmj. 2015 Aug 30;351:h4451

Reicher-Reiss H, Jonas M, Boyko V, Shotan A, Goldbourt U, Behar S. Are coronary patients at higher risk with digoxin therapy? An ongoing controversy. Int J Cardiol 1999;68:137-43

Muller JE, Turi ZG, Stone PH, et al. Digoxin therapy and mortality after myocardial infarction. Experience in the MILIS Study. N Engl J Med 1986;314:265-71

Leor J, Goldbourt U, Behar S, et al. Digoxin and mortality in survivors of acute myocardial infarction: observations in patients at low and intermediate risk. The SPRINT Study Group. Secondary Prevention Reinfarction Israeli Nifedipine Trial. Cardiovasc Drugs Ther 1995;9:609-17

Blackwood R, Mayou RA, Garnham JC, Armstrong C, Bryant B. Exercise capacity and quality of life in the treatment of heart failure. Clin Pharmacol Ther 1990;48:325-32

Van Veldhuisen DJ, Man in ‘t Veld AJ, Dunselman PH, et al. Double-blind placebo-controlled study of ibopamine and digoxin in patients with mild to moderate heart failure: results of the Dutch Ibopamine Multicenter Trial (DIMT). J Am Coll Cardiol1993; 22:1564-73

Kamei Y, Monden A, Matsumoto S, Kakimoto T, Matsumoto KI. The effects of over and under sampling on fault-prone module detection. In Empirical Software Engineering and Measurement, 2007. ESEM 2007. First International Symposium on 2007 Sep 20 (pp. 196-204). IEEE

Whitbeck MG, Charnigo RJ, Khairy P, Ziada K, Bailey AL, Zegarra MM, Shah J, Morales G, Macaulay T, Sorrell VL, Campbell CL. Increased mortality among patients taking digoxin—analysis from the AFFIRM study. European heart journal. 2012 Nov 27; 34(20):1481-8

Lopes RD, Rordorf R, De Ferrari GM, Leonardi S, Thomas L, Wojdyla DM, Ridefelt P, Lawrence JH, De Caterina R, Vinereanu D, Hanna M. Digoxin and mortality in patients with atrial fibrillation. Journal of the American College of Cardiology. 2018 Mar 13; 71(10):1063-74

Vamos M, Erath JW, Hohnloser SH. Digoxin-associated mortality: a systematic review and meta-analysis of the literature. European heart journal. 2015 May 4; 36(28):1831-8

Allen LA, Fonarow GC, Simon DN, Thomas LE, Marzec LN, Pokorney SD, Gersh BJ, Go AS, Hylek EM, Kowey PR, Mahaffey KW. Digoxin use and subsequent outcomes among patients in a contemporary atrial fibrillation cohort. Journal of the American College of Cardiology. 2015 Jun 30;65(25):2691-8

Friberg L, Hammar N, Rosenqvist M. Digoxin in atrial fibrillation: report from the Stockholm Cohort study of Atrial Fibrillation (SCAF). Heart. 2010 Feb 1; 96(4):275-80

Adedinsewo D, Xu J, Agasthi P, Oderinde A, Adekeye O, Sachdeva R, Rust G, Onwuanyi A. Effect of Digoxin Use Among Medicaid Enrollees With Atrial Fibrillation. Circulation: Arrhythmia and Electrophysiology. 2017 May 1; 10(5):e004573

Chao TF, Liu CJ, Tuan TC, Chen SJ, Wang KL, Lin YJ, Chang SL, Lo LW, Hu YF, Chen TJ, Chiang CE. Rate-control treatment and mortality in atrial fibrillation. Circulation. 2015 Sep 17: CIRCULATIONAHA-114

January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Journal of the American College of Cardiology. 2014 Dec 2; 64(21):e1-76

Biomedical Sciences