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Editorials

Digoxin

Quo Vadis?

John G.F. Cleland, MD and Damien Cullington, MD

From the Department of Cardiology, University of Hull, Kingston-Upon-Hull, United Kingdom.

Correspondence to John G.F. Cleland, MD, Department of Cardiology, University of Hull, Castle Hill Hospital, Kingston-Upon-Hull, Cottingham HU16 5JQ, United Kingdom. E-mail g.m.porter@hull.ac.uk

Key Words: Editorials • digoxin

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Despite more than 200 years of research, the role of digoxin in contemporary medicine remains controversial. It is an old drug but with a remarkably sophisticated and rather modern pharmacological profile. It was the first neuroendocrine modulator to enhance parasympathetic tone and possibly reduce sympathetic activity.¹ It is the only available oral inotropic agent. It is probably also a diuretic.² In common with many other agents for heart failure, good dose-ranging studies have not been conducted, and the optimal dose is uncertain. Well-designed randomized controlled trials conducted in the pre–β-blocker era suggested that digoxin could improve symptoms and exercise capacity,^3,4 but a large trial that enrolled patients mostly with mild symptoms suggested no overall effect on mortality, although it did report a substantial (28%) reduction in hospitalization for worsening heart failure.⁵ A small increase in sudden death was balanced by a reduction in death from worsening heart failure. Whether these benefits were mediated by changes in autonomic tone, in heart rate, in sodium balance, or through inotropic effects is unclear.

Article see p 90

At this time, the clinical community’s attention turned from the potential, but still equivocal, effects of digoxin on morbidity and mortality to the striking benefits of aldosterone receptor antagonists⁶ and β-blockers⁷ and, subsequently, cardiac resynchronization therapy⁸ on prognosis. Digoxin became largely ignored in discussions and debate, its use declined rapidly (Table and Figure), and the role of digoxin for managing heart failure was left unresolved.

View this table:   Table. Summary Characteristics of Landmark Trials of Heart Failure

 

View this table:   . . . [Full Text of this Article]

 

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