Clinical Use of Digitalis: A State of the Art Review

Thomas F. Whayne Jr


Am J Cardiovasc Drugs. 2018;18(6):427-440. 

In This Article

Abstract and Introduction


The history of digitalis is rich and interesting, with the first use usually attributed to William Withering and his study on the foxglove published in 1785. However, some knowledge of plants with digitalis-like effects used for congestive heart failure (CHF) was in evidence as early as Roman times. The active components of the foxglove (Digitalis purpurea and Digitalis lanata) are classified as cardiac glycosides or cardiotonic steroids and include the well-known digitalis leaf, digitoxin, and digoxin; ouabain is a rapid-acting glycoside usually obtained from Strophanthus gratus. These drugs are potent inhibitors of cellular membrane sodium–potassium adenosine triphosphatase (Na+/K+-ATPase). For most of the twentieth century, digitalis and its derivatives, especially digoxin, were the available standard of care for CHF. However, as the century closed, many doubts, especially regarding safety, were raised about their use as other treatments for CHF, such as decreasing the preload of the left ventricle, were developed. Careful attention is needed to maintain the serum digoxin level at ≤ 1.0 ng/ml because of the very narrow therapeutic window of the medication. Evidence for benefit exists for CHF with reduced ejection fraction (EF), also referred to as heart failure with reduced EF (HFrEF), especially when considering the combination of mortality, morbidity, and decreased hospitalizations. However, the major support for using digoxin is in atrial fibrillation (AF) with a rapid ventricular response when a rate control approach is planned. The strongest support of all for digoxin is for its use in rate control in AF in the presence of a marginal blood pressure, since all other rate control medications contribute to additional hypotension. In summary, these days, digoxin appears to be of most use in HFrEF and in AF with rapid ventricular response for rate control, especially when associated with hypotension. The valuable history of the foxglove continues; it has been modified but not relegated to the garden or the medical history book, as some would advocate.


Most clinicians, including those with medical history knowledge, credit William Withering with the discovery of digitalis. However, apparently this was not the case—important pharmacological effects had been associated with plants containing digitalis-like activity for approximately 2000 years.[1] However, in 1785, it was Withering, a highly regarded English botanist and physician, who published a summary study of 163 patients with "dropsy" to whom he had administered digitalis.[1] Thus began the epic clinical journey of a medication once considered essential in the care of the cardiac patient. The current story involves more controversy for a medication still esteemed more by senior clinicians. The purpose of this review is to assess the state of the art regarding digitalis use and where, when, and how this historic medication from the foxglove[2] should be used.