Is Digoxin Still Useful in Heart Disease?

foxglove plant
foxglove. itsabreeze photography/Getty images 

For over 200 years, digitalis (a substance derived from the foxglove plant), has been a mainstay in the treatment of heart disease—in particular, heart failure and atrial fibrillation. Digoxin (by far, the most commonly used form of digitalis) is still widely prescribed for these two cardiac conditions.

In recent decades, however, experts have strongly questioned whether digoxin still ought to be used in the treatment of heart disease.

There are two general reasons for this recent skepticism regarding digoxin. First, several newer drugs have been developed whose efficacy has been proven in clinical trials, whereas randomized trials demonstrating the benefits of digoxin have been relatively few. So the actual clinical benefits of digoxin have been questioned.

Second, digitalis toxicity can be quite difficult to avoid, and it can be quite dangerous. In most cases, other drugs with less potential for toxicity can be used instead of digoxin. 

Despite these problems, digoxin can still be useful in some people with heart failure or atrial fibrillation. 

How Does Digoxin Work?

Digoxin has two major effects on the heart.

First, it inhibits certain pumps in the cardiac cell membranes, reducing the movement of sodium from the inside of cells to the outside of cells. This action has the effect of improving the force of contraction of cardiac muscle.

Thus, a weakened heart muscle can pump a bit more effectively when digoxin is administered.

Second, digoxin affects autonomic tone, decreasing sympathetic (“fight or flight”) and increasing parasympathetic (vagal) tone. These changes in autonomic tone reduce the conduction of cardiac electrical impulses through the AV node and therefore tend to slow the heart rate in people who have atrial fibrillation.

In summary, digoxin can improve cardiac muscle contraction in people with heart failure and can slow the heart rate in people with atrial fibrillation.

Digoxin Toxicity

The toxic effects of digoxin are related to the blood levels of the drug. Unfortunately, the therapeutic drug levels with digoxin are not that much different than the toxic blood levels—so the difference between taking “enough” digoxin and taking too much digoxin is often very small. This “narrow therapeutic window” makes the safe use of digoxin relatively difficult for many people.

Digoxin toxicity is more likely in people who develop kidney problems or low potassium levels—both of which are relatively common in people who have heart failure and who are being treated with diuretics.

The toxic effects of digoxin include life-threatening cardiac arrhythmias, particularly ventricular tachycardia and ventricular fibrillation, severe bradycardia (slow heart rate), heart block, loss of appetite, nausea or vomiting, and neurological problems including confusion and visual disturbances. Notably, at least 30 percent of people with toxic digoxin levels experience no symptoms. This means that life-threatening cardiac arrhythmias may occur in these people without any warning.

When a person takes digoxin, blood levels are usually measured periodically to attempt to stay within the narrow therapeutic window.

Digoxin in the Treatment of Heart Failure

As recently as 30 years ago, digoxin (along with diuretics) was the mainstay of treatment in people with heart failure due to dilated cardiomyopathy—that is, heart failure caused by a weakening of the heart muscle, characterized by a reduced ejection fraction.

But since that time several new treatments have been developed for heart failure whose efficacy has been clearly demonstrated in numerous randomized clinical trials. Drugs that have been shown to improve symptoms and increase survival include beta blockersACE inhibitorsARB agents, and (most recently) the combination of an ARB drug and a neprilysin inhibitor marketed as Entresto.

In addition, many people with congestive heart failure are candidates for cardiac resynchronization therapy, a treatment that can also significantly reduce symptoms and improve survival.

Clinical trials have shown that, in people with heart failure due to dilated cardiomyopathy, digoxin appears to improve the symptoms of heart failure and reduce the need for hospitalization. However, in contrast to the other therapies now commonly used for heart failure, digoxin does not seem to improve survival.

Most experts now recommend using digoxin in people with heart failure only as a second-line or third-line treatment, if at all. That is, digoxin is generally recommended only if a person with heart failure continues having significant symptoms despite optimal therapy that includes a beta blocker, ACE inhibitor or ARB drug, diuretics, and/or Entresto.

Digoxin offers no benefit in treating people who have heart failure with a preserved ejection fraction—that is, people with diastolic heart failure. Digoxin is also not useful in stabilizing people with acute heart failure. Its use should be limited to managing those with chronic symptoms of dilated cardiomyopathy heart failure.

Digoxin in the Treatment of Atrial Fibrillation

As noted earlier, digoxin slows the conduction of electrical impulses through the AV node, and as a result, it can slow the heart rate in people who have atrial fibrillation. Since a rapid heart rate is a chief cause of symptoms in people with atrial fibrillation, digoxin can be useful in providing some relief of symptoms.

However, digoxin tends to be substantially less effective in relieving symptoms than the other two classes of drugs now commonly used to slow the heart rate in atrial fibrillation, namely, beta blockers, and calcium channel blockers. These two classes of drugs produce slowing of the heart rate both at rest and during exercise, whereas digoxin slows the heart rate only at rest. Because many people with atrial fibrillation complain mostly of poor exercise tolerance, caused by a rapid increase in heart rate with even mild exercise, digoxin provides little relief in their symptoms.

Furthermore, there is now evidence that using digoxin for rate control in people with atrial fibrillation is associated with an increase in mortality. In particular, a 2017 clinical trial suggests that this increase in mortality is directly proportional to digoxin blood levels—that is, the higher the blood levels, the higher the risk. While the cause of the apparently elevated risk of dying with digoxin is not certain, it is likely that it is due to a higher risk of sudden death from cardiac arrhythmias.

Most experts are now at least somewhat reluctant to recommend using digoxin for controlling the heart rate in people with atrial fibrillation. However, digoxin may still be a reasonable option if a person with atrial fibrillation is having persistent and significant symptoms at rest, that are not relieved by a combination of beta blockers and calcium channel blockers.

A Word From Verywell

Not long ago, digoxin was a mainstay of therapy for both heart failure and atrial fibrillation. However, in recent decades newer drugs have been developed that are more effective, and safer to use. Most experts now recommend using digoxin only in individuals in whom this drug is likely to offer some particular and substantial benefit. And when it is used, it must be used cautiously. 

Sources:

Ambrosy AP, Butler J, Ahmed A, et al. The Use Of Digoxin In Patients With Worsening Chronic Heart Failure: Reconsidering An Old Drug To Reduce Hospital Admissions. J Am Coll Cardiol 2014; 63:1823.

Lopes R, Gibson CM. ARISTOTLE: Digoxin And Mortality In Patients With Atrial Fibrillation With And Without Heart Failure: Does Serum Digoxin Concentration Matter? Program and abstracts of the American College of Cardiology 66th Annual Scientific Session & Expo; March 17-19, 2017; Washington, DC. Late-breaking clinical trial.

Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines For The Diagnosis And Treatment Of Acute And Chronic Heart Failure: The Task Force For The Diagnosis And Treatment Of Acute And Chronic Heart Failure Of The European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2016; 37:2129.