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Digoxin is a cardiac glycoside originally derived from the foxglove plant. The utility of foxglove extract was first described for the treatment of “dropsy” and other diseases by the English physician, William Withering in 1785.1 Dropsy is an old term for edema so these patients likely had congestive heart failure. Digoxin was first isolated from foxglove in 1930.1
I grew up with digoxin as a medical resident from 1973 to 1975 when the only agents to control the ventricular response in afib were digoxin and the new drug, propranolol, which was approved by the FDA in 1967. Despite digoxin’s long-time use, a JACC editorial said that digoxin should be left out of our medical armamentarium.( Turakhia MP. Digoxin in Atrial Fibrillation?: Leave it Out of the Medicine Cabinet. J Am Coll Cardiol. 2018 Mar 13;71(10):1075-1077) I am not an electrophysiologist, but let me make the case for the alternative point of view – a view with support from recent literature.2 You ultimately have to decide what you’ll do, but like the 1972 “Mikey” commercial for Life cereal, “Try It You Might Like It”.
Digoxin has three cardiac effects: 1- It increases cardiac contractility. 2- It decreases atrial to ventricular (A-V) conduction . 3- It increases the automaticity of all cardiac pacemakers This decrease in A-V conduction and increase in automaticity means that dig toxicity can present as complete A-V block with an accelerated junctional rate. Indeed, I was taught as a resident to ignore slow irregular HRs in afib patients on digoxin because that’s what we wanted, but to worry about regularization of the HR. A regular HR could indicate that the high doses of dig we were forced to use to control the ventricular response had produced complete A-V block with an accelerated junction escape rhythm. The junctional escape could be faster than the usual ~40 beats per minute.(BPM) because the digoxin increased the node’s automaticity.
I am not a heart failure expert so I primarily use digoxin to decrease A-V conduction and to help control HRs in afib and aflutter. The sinus rhythm HR at rest is largely due to vagal tone. There are not a lot of catecholamines floating around at rest. This dearth of catecholamines at rest explains why beta blockers often do not decrease the HR in afib and flutter to the desired value of at least <90 beats per minute (BPM). Digoxin, however, by decreasing A-V conduction is often extremely effective in decreasing the ventricular response in afib and aflutter. This is especially true in aflutter, which often does not respond well to beta blockers alone.
Digoxin increased vagal tone but does not reduce the resting HR when patients are in sinus rhythm probably because vagal tone is already high at rest. So patients with paroxysmal afib get slower A-V conduction during afib, but little additional bradycardia when in sinus rhythm. Digoxin also does not reduce exercise HRs either in sinus rhythm or in afib because exercise HRs are primarily due to increased adrenergic activity.3 This is a slight benefit for paroxysmal afib patients because their exercise HR is unaffected when they are in sinus rhythm. Digoxin can also be used alone to control the HR in afib, but its best use is in combination with beta blockage since together they can control both the resting and exercise afib HRs.
So, why is there so much reluctance to use a drug that has been around for almost 240 years. I think because of bad studies. The “bad studies” were reports of increased mortality among patients with myocardial infarctions (MIs) who were treated with digoxin. But who gets treated with digoxin during an MI? Patients with afib. And which MI patients get afib? Patients with anterior wall MIs because anterior wall MIs get more left ventricular dysfunction, which increases left atrial pressure, which increases the risk of afib. And which MI patients have a worse prognosis? Those with anterior wall MIs. So digoxin looked bad because it was used in a bad situation. There are also studies in patients with afib showing that patients on digoxin did worse with the drug, but these studies used statistical controls and did not randomize patients.
Some worries about digoxin should have disappeared with the Digitalis Investigation Group’s study of digoxin risk/benefit in heart failure (HF).4 This group randomized HF patients to digoxin (n=3,397) or placebo (n=3,403) and followed them for an average of 37 months. The total death rates were similar for digoxin and placebo, 34.8 vs 35.1%. There was a trend (p=0.06) toward fewer HF deaths with digoxin, but there was a significant 6% decrease in total hospitalizations and a 28% decrease in HF hospitalizations (p<0.001). My take is that digoxin did not save lives, but didn’t kill anybody and helped patients with HR. Consequently, you don’t need to retain a malpractice lawyer to use it.
I think that’s enough for now. I don’t want these pieces to be too long because everyone is busy. The next post will address “What do you need to know to use digoxin”?
2. Kotecha D, Bunting KV, Gill SK, et al. Effect of Digoxin vs Bisoprolol for Heart Rate Control in Atrial Fibrillation on Patient-Reported Quality of Life: The RATE-AF Randomized Clinical Trial. Rate Control Therapy Evaluation in Permanent Atrial Fibrillation (RATE-AF) Team.JAMA. 2020 Dec 22;324(24):2497-2508. PMID: 33351042
3. Matsuda M, Matsuda Y, Yamagishi T, et al. Effects of digoxin, propranolol, and verapamil on exercise in patients with chronic isolated atrial fibrillation. . 1991 Jun;25(6):453-7. PMID: 1889058
4. Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 1997 Feb 20;336(8):525-33.PMID: 9036306
Great insights. I do see a resurgence of digoxin use in the hospital setting in my practice, and surprisingly so, from the EP peeps, probably influenced by the recent HF trials. I keep it as part of my armamentarium, and when deployed, can yield positive short term outcomes in this HF population.
Paul,
This is great analysis of the whole story, and great writing.
I completely agree with you.
A specific area where it is very useful is for patients with a fib or flutter with increased HR who have low BP, and cannot tolerate BB or Ca Ch B.
Thank you for writing this.
Ara