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Re: Role of digoxin in chronic heart failure in the developing nation

Dear Editors,

The recent editorial review of the 2005 European Society of Cardiology (ESC) chronic heart failure guidelines by Brady and Poole- Wilson commented that “digoxin is rightly consigned to be used only in patients with heart failure and atrial fibrillation (AF), and should be combined with a ß blocker.”1

However, the ESC guidelines also state that while digoxin has no effect on mortality, it “may reduce hospitalizations and, particularly, worsening heart failure hospitalizations, in the patients with heart failure caused by left ventricular systolic dysfunction and sinus rhythm treated with ACE-inhibitors, beta-blockers, diuretics and in severe heart failure, spironolactone” which was a Class IIa recommendation (weight of evidence/opinion is in favour of usefulness/efficacy), based on Level A evidence (data derived from multiple randomized clinical trials or meta- analyses).2

The 2005 American College of Cardiology / American Heart Association chronic heart failure guidelines consider the use of digoxin to reduce hospitalizations due to worsening heart failure a Class IIa (weight of evidence/opinion is in favor of usefulness/efficacy) based on Level B evidence (data derived from a single randomized trial, or nonrandomized studies).3

The 2006 Heart Failure Society of American guidelines for chronic heart failure recommend that digoxin “should be considered” for patients with systolic heart failure who have signs or symptoms of heart failure while receiving standard therapy, including ACE inhibitors and b- blockers.4

In the Digitalis Investigation Group trial (N=6,800), in ambulatory chronic heart failure patients with normal sinus rhythm, while digoxin did not reduce mortality, its use was associated with significant reduction of heart failure hospitalizations, which was unaffected by serum digoxin concentraion.5, 6 Hospitalization is a major complications of heart failure, both from the patients and health services resource utilization perspective. Discouraging digoxin use in heart failure patients in normal sinus rhythm, “ignores, or at least minimizes, the very substantial benefit in morbidity seen with digoxin (number needed to treat for 3 years to avoid one costly heart failure hospitalization = 10–12).”7

Digoxin is also one of the most inexpensive heart failure drugs and is likely to have a favorable cost-effectiveness ratio both in the developed and developing nations.7 This is particularly important for heart failure patients in the developing nations, who might not be able to afford other heart failure medications such as ACE inhibitors and beta- blockers. As clinicians in the developing nations follow BMJ journals, an unqualified disapproval of the role of digoxin in heart failure may adversely affect the health of millions of heart failure patients in those countries. As recommended in all three major chronic heart failure guidelines, digoxin should be used in low doses for heart failure patients who are symptomatic despite other therapy including ACE inhibitors / angiotensin receptor blockers, and beta blockers.2-4

Ali Ahmed, MD, MPH University of Alabama at Birmingham Veterans Affairs Medical Center Birmingham AL 35294-2041 USA

References

1. Brady AJB, Poole-Wilson PA. ESC-CHF: guidelines for the aspirational and the practical. Heart. 2006;92:437-440.

2. Swedberg K, Cleland J, Dargie H, et al. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J. Jun 2005;26(11):1115- 1140.

3. Hunt SA, Abraham WT, Chin MH, et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). Developed in Collaboration With the American College of Chest Physicians and the International Society for Heart and Lung Transplantation. Endorsed by the Heart Rhythm Society. Circulation. Sep 13 2005.

4. Adams K, Lindenfeld J, Arnold J, et al. Executive Summary: HFSA 2006 Comprehensive Heart Failure Practice Guideline. J Cardiac Failure. 2006;12:10-38.

5. The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. Feb 20 1997;336(8):525-533.

6. Ahmed A, Rich MW, Love TE, et al. Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial. Eur Heart J. Jan 2006;27(2):178-186.