Digoxin and mortality in atrial fibrillation: a prospective cohort study
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The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study showed that rhythm-control treatment of patients with atrial fibrillation (AF) offered no survival advantage over a rate-control strategy. In a subgroup analysis of that study, it was found that digoxin increased the death rate [relative risk (RR) = 1.42), but it was suggested that this may have been attributable to prescription of digoxin for patients at greater risk of death, such as those with congestive heart failure (CHF). No study has investigated a priori the effect of digoxin on mortality in patients with AF. This study aimed to address this question.
Using data from the Registry of Information and Knowledge about Swedish Heart Intensive care Admissions (RIKS-HIA), we studied the 1-year mortality among patients admitted to coronary care units with AF, CHF, or AF+CHF with or without digoxin (n = 60,764) during 1995–2003. Adjustment for differences in background characteristics and other medications and treatments was made by propensity scoring.
Twenty percent of patients with AF without CHF in this cohort were discharged with digoxin. This group had a higher mortality rate than the corresponding group not given digoxin [adjusted RR 1.42 (95% CI 1.29–1.56)], whereas no such difference was seen among patients with CHF with or without AF, although these patients had a nearly three-times higher mortality.
The results suggest that long-term therapy with digoxin is an independent risk factor for death in patients with AF without CHF.
KeywordsDigoxin Atrial fibrillation Heart failure Mortality RIKS-HIA
We thank the Swedish Heart Lung Foundation for funding this study (grant #20040494). We also thank Karl Michaelsson, MD, PhD, at Uppsala University Hospital, for valuable feedback concerning the statistical analyses.
Conflict of Interest Statement
This study was funded partly by the Swedish Heart-Lung Foundation, but the foundation had no active role in the study.
- 2.Hornestam B, on behalf of the Digitalis in Acute Atrial Fibrillation (DAAF) Trial Group (1997) Intravenous digoxin in acute atrial fibrillation. Results of a randomized, placebo-controlled multicentre trial in 239 patients. Eur Heart J 18(4):649–654Google Scholar
- 3.Adams KF Jr, Patterson JH, Gattis WA, O’Connor CM, Lee CR, Schwartz TA, Gheorghiade M (2005) Relationship of serum digoxin concentration to mortality and morbidity in women in the digitalis investigation group trial: a retrospective analysis. J Am Coll Cardiol 46(3):497–504PubMedCrossRefGoogle Scholar
- 5.Corley SD, Epstein AE, DiMarco JP, Domanski MJ, Geller N, Greene HL, Josephson RA, Kellen JC, Klein RC, Krahn AD, Mickel M, Mitchell LB, Nelson JD, Rosenberg Y, Schron E, Shemanski L, Waldo AL, Wyse DG (2004) Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Study. Circulation 109(12):1509–1513PubMedCrossRefGoogle Scholar
- 8.Fuster V, Ryden LE, Asinger RW, Cannom DS, Crijns HJ, Frye RL, Halperin JL, Kay GN, Klein WW, Levy S, McNamara RL, Prystowsky EN, Wann LS, Wyse DG (2001) ACC/AHA/ESC guidelines 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 European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to develop guidelines for the management of patients with atrial fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology. Eur Heart J 22(20):1852–1923PubMedCrossRefGoogle Scholar
- 22.Packer M, Gheorghiade M, Young JB, Costantini PJ, Adams KF, Cody RJ, Smith LK, Van Voorhees L, Gourley LA, Jolly MK (1993) Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. RADIANCE Study. N Engl J Med 329(1):1–7PubMedCrossRefGoogle Scholar
- 36.Tauke J, Goldstein S, Gheorghiade M (1994) Digoxin for chronic heart failure: a review of the randomized controlled trials with special attention to the PROVED (Prospective Randomized Study of Ventricular Failure and the Efficacy of Digoxin) and RADIANCE (Randomized Assessment of Digoxin on Inhibitors of the angiotensin Converting Enzyme) trials. Prog Cardiovasc Dis 37(1):49–58PubMedCrossRefGoogle Scholar
- 37.Uretsky BF, Young JB, Shahidi FE, Yellen LG, Harrison MC, Jolly MK (1993) Randomized study assessing the effect of digoxin withdrawal in patients with mild to moderate chronic congestive heart failure: results of the PROVED trial. PROVED Investigative Group. J Am Coll Cardiol 22(4):955–962PubMedCrossRefGoogle Scholar
- 39.Vardas PE, Kanoupakis EM, Kochiadakis GE, Simantirakis EN, Marketou ME, Chlouverakis GI (1998) Effects of long-term digoxin therapy on heart rate variability, baroreceptor sensitivity, and exercise capacity in patients with heart failure. Cardiovasc Drugs Ther 12(1):47–55PubMedCrossRefGoogle Scholar