Digoxin at the new Millenium

by Jerry Sobieraj, MD ©2003

Digoxin is a medication that previosly had a high use for its inotropic effect. Attempts to show its usefulness in CHF were largely observational, until a large VA trial was published in 1999. The quality of life benefit has been extolled as a reason to use digoxin in people with CHF. The lack of a mortality benefit is ignored. I believe this is due to the long history digoxin has had in cardiology, and not to any substantiated benefit, especially in the context of CHF. In August 1983, when I was a medical student working at Beth Israel, William Grossman, who was chief of cardiology then, told me "digoxin was poison". At the time he believed it would be supplanted by other more potent inotropes. This turned out to not be the case with afterload reduction by ACEI the break through of the 1980s, and a better understanding of how to manage prolonged excess catechols in the 1990s.

In fact, the love with digoxin has an irrational side to it. Not only did it fail to show a mortality benefit in the VA trial, the cardiology community (at least the one we see at BMC) has been slow to adopt the use of another common agent which has shown a clear mortality benefit it patients with class III and IV heart failure. The study by Pitts, et al published in the August 1999 NEJM showed an absolute (not relative) mortality benefit of 30% after only 18 months of therapy. The use of spironolactone hasn't been adopted because it is unclear to cardiologists what the mechanism of this benefit may be (Pitts data suggested it wasn't due to its antagonism of aldosterone). Of course, we often use drugs that we don't understand the mechanism of, but due to clinical trials, they have shown their efficacy.

Digoxin does indeed still have clinical utility. However, this is not in CHF, but in rate control with atrial tachyarrhythmias. At times, COPD and reactive airways may limit your use of a beta blocker for rate control. A rate controlling calcium channel blocker like diltizem or verapamil may be considered when AV node block is required. Yet, digoxin would be a fine alternative, and espeically if the doses of verapamil and diltiazem were having an adverse effect on the blood pressure. So indeed, digoxin is still useful, but largely in the context of rate control when AV nodal block can accomplish that end.

As taken from Goodman and Gillman (1985), the following is noted for digoxin

avg digitalizing dose 0.75-1.5 po, 0.5-1.0 IV
onset of action: po 1.5-6hr, iv 5-30 min
peak effect: po 4-6 hr, iv 1.5-3 hr

Digoxin increases myocardial contractility in the face of beta blockade, which suggests a direct inotropic effect, as LVEDD is not changed. However, there is a reflex increase in SVR (systemic vascular resistance), and thus, no resultant increase in CO. The increase in SVR is due to a direct effect of dig on resistance vessels. A small decrease in Sinus Rate due to reflex effects also occurs. "Most of the clnically important effects of digitalis on the rate of formation of impulses by the SA node are due to indirect effects that the drug exerts through the parasympathetic and sympathetic nervous systems." "The AV node is strongly influenced by the indirect actions of digitalis. The enhanced vagal activity and the decrease in sensitivity to catecholamines have pronounced effects on both the generation of AV nodal AP (action potential) and the transmission of impulses through the node."

"If it is certain that the patient has NOT been taking digitalis, 1.0 mg of digoxin can be given intravenously over a period of 10-20 minutes. Very often the loading dose is divided into two doses of 0.5 mg given 3-4 hrs apart." "In approx 10% of patients, a substantial fraction of ingested digoxin is converted to inactive products by intestinal microorganisms."