One of my colleagues here in Tucson thinks that digitalis therapy should be relegated to the medical trash heap alongside calomel, bleeding, and purging. I disagree, although digitalis therapy is certainly not as au courant today as it was when I was in training decades ago. Indeed, at that time, various forms of digitalis therapy were the mainstays of the therapeutic armamentarium for patients with clinical heart failure. Of course, this was an era before beta-blockers, and renin-angiotensin and mineralocorticoid blockade were available and shown to reduce mortality and improve the quality of life of patients with heart failure. In that bygone era, we did have diuretics and nitrates, but digitalization of the patient was the cornerstone of all therapeutic approaches for patients with heart failure.
A number of well-designed interventional trials in those years and subsequently did demonstrate that digitalis therapy improved hemodynamics and clinical status in patients with heart failure.1, 2, 3, 4, 5 However, many subsequent randomized, double-blind, placebo-controlled trials with large numbers of patients clearly established that beta-blockers, angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and mineralocorticoid blockers led to substantial and statistically significant improvements in mortality and clinical status in patients with heart failure. Indeed, the first time that I observed normalization of left ventricular function in a patient with prior severe heart failure during oral carvedilol therapy, I thought that the original echocardiographic report was in error. Subsequently, I have seen this remarkable therapeutic response many times in patients whose left ventricular ejection fraction had initially been <25%. By comparison with this remarkable improvement in clinical status, digitalis therapy was indeed a very poor “country cousin.” Similar impressive clinical responses also were demonstrated with other beta-blockers (bisoprolol, long-acting metoprolol), ACEI/ARB, and the mineralocorticoid blockers spironolactone and eplerenone.6 Given these recent trials, what if any role is left for digitalis therapy in the management of patients with heart failure?
In my opinion, there is still a place for digitalis therapy in our current era of modern pharmacotherapy. For example, in selected individuals with chronic atrial fibrillation and contraindications to beta-blockers or nondihydropyridine calcium blockers, oral digoxin has been an effective therapeutic option for many decades to control heart rate. For patients with heart failure who remain symptomatic despite an excellent regimen of the above-mentioned evidence-based drug therapy, digoxin therapy has been shown to be of benefit.7, 8, 9 In the large randomized and double-blind Digitalis Investigation Group trial, therapy with digoxin was shown to reduce subsequent heart failure hospital admissions. Recent reports using data from this large, randomized, double-blind trial showed that improvement in readmission rates to the hospital, both all-cause and cardiovascular, were significantly reduced with digoxin therapy in patients with decreased left ventricular function.8, 9 Interestingly, reduced mortality was seen with digoxin administration in patients whose serum digoxin level was <1.0 ng/mL.10 The latter observation was the result of a post hoc sub-study, and so this piece of information is not as reliable as the former result, that is, reduced hospital admission. Contrary to what I had been taught during my training, higher therapeutic blood levels of digoxin were observed to be deleterious.
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–Joseph S. Alpert, MD (Editor-in-Chief, The American Journal of Medicine)
Professor of Medicine, University of Arizona College of Medicine, Tucson
This article originally appeared in the June 2014 issue of The American Journal of Medicine.
