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Digoxin and quality of life in heart failure
Journal of Cardiac Failure Vol. 9 No. 4 2003
Letter to the Editor Digoxin and Quality of Life in Heart Failure
2. Hunt SA, Baker DW, Chin MH, Cinquegrani MP, Feldman AM, Francis GS, American College of Cardiology/American Heart Association. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol 2001;38(7):2101-13.
To the Editor: The study by Lader et al demonstrates that treatment with digoxin does not substantially improve the quality of life or exercise tolerance of stable outpatients with heart failure.1 Although we are pleased that the Digitalis Investigation Group (DIG) trial’s quality of life substudy results have been published, we are curious why this study was published 4 full years after the DIG trial’s main results. This is unfortunate given that, in the interim, national guidelines have continued to endorse digoxin, in part because of its purported beneficial effects on symptom relief and quality of life.2 We are concerned that the broader implications of Lader et al’s findings may be overlooked by most clinicians. The absence of an improvement in quality of life and an overall neutral effect on all-cause mortality raise concerns about the clinical benefit of digoxin therapy. This concern is all the more compelling given our recently published secondary analyses that found evidence of digoxin-associated harm in women and identified an extremely narrow therapeutic window for digoxin.3,4 Collectively, this body of evidence raises the question of what role, if any, digoxin has in the contemporary management of heart failure patients. Current American College of Cardiology/American Heart Association guidelines recommend the routine use of digoxin in patients with symptomatic heart failure and depressed systolic function,2 but the only apparent benefit of digoxin is a modest reduction in the DIG trial’s secondary endpoint of hospitalizations resulting from worsening heart failure. Further, it is unclear whether this presumed benefit would be observed in patients receiving state of the art therapy including angiotensin-converting enzyme inhibitors, -blockers, and spironolactone. Given the digoxin-associated harms in women, the limited range of serum concentrations in which digoxin therapy may be safe, the lack of an overall mortality benefit, and Lader et al’s findings of no substantive improvement in quality of life, we believe the role of digoxin in the treatment of patients with heart failure merits a thorough reexamination.
3. Rathore SS, Curtis JP, Wang Y, Bristow MR, Krumholz HM Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA 2003;289(7):871-8. 4. Rathore SS, Wang Y, Krumholz HM Sex-based differences in the effect of digoxin for the treatment of heart failure. New Engl J Med 2002;347(18):1043-11.
doi:10.1054/jcaf.2003.53
Reply: We read the letter of Curtis and Rathore with interest. It is true that in the Digitalis Investigation Group (DIG) trial there was no change in health-related quality of life as we measured it, but there was clearly a reduction in hospitalizations and no overall effect on mortality.1 We respect the DIG’s finding of an increased risk of harm of digitalis therapy in women, but must view it with the usual caution of any post-hoc analysis. As new data become available, we must continue to reevaluate our therapies—but taken in the larger sense, there is still evidence that digoxin is a useful and reasonably safe agent, and probably still deserves a place in the current guidelines for the treatment of heart failure. We acknowledge the delay between the publication of the main trial data and our report, but that reflects the exigencies of collaborative work and editorial input. Ellis Lader, MD Kingston, NY Susan Czajkowski, PhD Sally Hunsberger, PhD Bethesda, MD
Jeptha P. Curtis, MD Saif S. Rathore, MPH New Haven, CT
Reference 1. The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with congestive heart failure. N Engl J Med 1997;336:525-33.
References 1. Lader E, Egan D, Hunsberger S, Garg R, Czajkowski S, McSherry F The effect of digoxin on the quality of life in patients with heart failure. J Cardiac Fail 2003;9(1):4-12.
doi: 10.1054/jcaf.2003.54
345
Letter to the Editor Digoxin and Quality of Life in Heart Failure
2. Hunt SA, Baker DW, Chin MH, Cinquegrani MP, Feldman AM, Francis GS, American College of Cardiology/American Heart Association. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol 2001;38(7):2101-13.
To the Editor: The study by Lader et al demonstrates that treatment with digoxin does not substantially improve the quality of life or exercise tolerance of stable outpatients with heart failure.1 Although we are pleased that the Digitalis Investigation Group (DIG) trial’s quality of life substudy results have been published, we are curious why this study was published 4 full years after the DIG trial’s main results. This is unfortunate given that, in the interim, national guidelines have continued to endorse digoxin, in part because of its purported beneficial effects on symptom relief and quality of life.2 We are concerned that the broader implications of Lader et al’s findings may be overlooked by most clinicians. The absence of an improvement in quality of life and an overall neutral effect on all-cause mortality raise concerns about the clinical benefit of digoxin therapy. This concern is all the more compelling given our recently published secondary analyses that found evidence of digoxin-associated harm in women and identified an extremely narrow therapeutic window for digoxin.3,4 Collectively, this body of evidence raises the question of what role, if any, digoxin has in the contemporary management of heart failure patients. Current American College of Cardiology/American Heart Association guidelines recommend the routine use of digoxin in patients with symptomatic heart failure and depressed systolic function,2 but the only apparent benefit of digoxin is a modest reduction in the DIG trial’s secondary endpoint of hospitalizations resulting from worsening heart failure. Further, it is unclear whether this presumed benefit would be observed in patients receiving state of the art therapy including angiotensin-converting enzyme inhibitors, -blockers, and spironolactone. Given the digoxin-associated harms in women, the limited range of serum concentrations in which digoxin therapy may be safe, the lack of an overall mortality benefit, and Lader et al’s findings of no substantive improvement in quality of life, we believe the role of digoxin in the treatment of patients with heart failure merits a thorough reexamination.
3. Rathore SS, Curtis JP, Wang Y, Bristow MR, Krumholz HM Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA 2003;289(7):871-8. 4. Rathore SS, Wang Y, Krumholz HM Sex-based differences in the effect of digoxin for the treatment of heart failure. New Engl J Med 2002;347(18):1043-11.
doi:10.1054/jcaf.2003.53
Reply: We read the letter of Curtis and Rathore with interest. It is true that in the Digitalis Investigation Group (DIG) trial there was no change in health-related quality of life as we measured it, but there was clearly a reduction in hospitalizations and no overall effect on mortality.1 We respect the DIG’s finding of an increased risk of harm of digitalis therapy in women, but must view it with the usual caution of any post-hoc analysis. As new data become available, we must continue to reevaluate our therapies—but taken in the larger sense, there is still evidence that digoxin is a useful and reasonably safe agent, and probably still deserves a place in the current guidelines for the treatment of heart failure. We acknowledge the delay between the publication of the main trial data and our report, but that reflects the exigencies of collaborative work and editorial input. Ellis Lader, MD Kingston, NY Susan Czajkowski, PhD Sally Hunsberger, PhD Bethesda, MD
Jeptha P. Curtis, MD Saif S. Rathore, MPH New Haven, CT
Reference 1. The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with congestive heart failure. N Engl J Med 1997;336:525-33.
References 1. Lader E, Egan D, Hunsberger S, Garg R, Czajkowski S, McSherry F The effect of digoxin on the quality of life in patients with heart failure. J Cardiac Fail 2003;9(1):4-12.
doi: 10.1054/jcaf.2003.54
345