Clinical benefits of low serum digoxin concentrations in heart failure
Kirkwood F. Adams, Jr, MD, FACC*,*,
Mihai Gheorghiade, MD, FACC ,
Barry F. Uretsky, MD, FACC||,
J. Herbert Patterson, PharmD ,
Todd A. Schwartz, MS and
James B. Young, MD, FACC¶
* Departments of Medicine and Radiology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
Departments of Medicine and Radiology, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA
Department of Biostatistics, School of Public Health, University of North Carolina, Chapel Hill, North Carolina, USA
Department of Medicine, Northwestern University Medical School, Chicago, Illinois, USA
|| Department of Medicine, University of Texas Medical Branch, Galveston, Texas, USA
¶ Department of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio, USA
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Figure 1 Study schema of the Prospective Randomized study Of Ventricular failure (PROVED) and Randomized Assessment of Digoxin on Inhibitors of the Angiotensin-Converting Enzyme (RADIANCE) trials. After a period of single-blinded stabilization, the patients were randomized to continue or discontinue digoxin, while maintaining background therapy as indicated. The occurrence of treatment failure was determined by an Events Committee that was blinded to treatment assignment. ACEI = angiotensin-converting enzyme inhibitor; Chg Dig = investigator change in digoxin dose; CXR = chest x-ray; Echo = echocardiogram; ER = emergency room; ETT = maximal exercise treadmill test; HF = heart failure; Hx = history; LVEF = left ventricular ejection fraction; NYHA = New York Heart Association functional class; PE = physical examination; SDC = serum digoxin concentration; Wk = week; 6 MinWalk = 6-min walk test.
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Figure 2 Adjusted likelihood of worsening heart failure (HF) in the four patient groups defined by either withdrawal from digoxin or serum digoxin concentration (SDC) at randomization in those who continued the drug. Patients who continued digoxin in any category of serum concentration were significantly less likely (all p < 0.02) to experience treatment failure than patients withdrawn from digoxin.
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Figure 3 Changes in maximal exercise treadmill test (ETT) duration in the four patient groups analyzed in the study. At the end of 12 weeks, patients who continued digoxin in each of the serum concentration groups had a significantly better exercise capacity than patients who discontinued digoxin (*p value for all three serum digoxin groups vs. placebo [digoxin withdrawal]). SDC = serum digoxin concentration.
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Figure 4 Changes in left ventricular ejection fraction (LVEF) from randomization to the final study measurement in the four patient groups analyzed in the study. Left ventricular ejection fraction declined significantly in patients who discontinued digoxin (Dig), compared with patients who continued digoxin, regardless of the serum concentration at randomization (*all p < 0.005). SDC = serum digoxin concentration.
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