Pushback on Digoxin

Just Try it, You Might Like It

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I get a lot of pushback about my recommendation that clinicians consider prescribing digoxin to control rapid atrial fibrillation.  Some of this comes from people I really respect, like Andy Epstein, MD, an excellent electrophysiologist at Penn and a friend for years.  He tells me that digoxin is rarely used at Penn by either the electrophysiology or heart failure groups.  That is also similar to my experience at Mass General Hospital (MGH) in Boston.  When I stepped down from being Chief of Cardiology at Hartford Hospital, I spent three years doing some attending on the consult service and stepdown unit am MGH.  Almost no one used digoxin and it was difficult to get pharmacy to allow digoxin loading, which I do as 0.25 mg x 3 doses, spread over 3 hours. On the other hand, an electrophysiologist of about my vintage,  Jeff Kluger, MD, who is at Hartford Hospital and whom I trust a lot uses digoxin in a manner similar to what I do.

Frankly,  writing a blog called “500 Rules of Cardiology” is incredibly presumptuous on my part.  All I ask is that you read it and think about it.  The next time you have a hospitalized patient with rapid Afib or Aflutter, not well-controlled on beta blockers, think about trying digoxin.  Patients teach you medicine, and I suspect that this little trial might be educational.  Here are my reasons. 

I always like to think about treatments by reviewing the physiology to ensure that the treatment makes physiological sense.  Resting heart rate is largely determined by vagal tone, because there are not a lot of catecholamines floating around at rest.  Digoxin works by increasing vagal tone - it does not depend on blocking catecholamines.  Beta blockers work by blocking catecholamines, so are best at slowing exercise heart rates.  You get some reduction in the Afib conduction rates at rest with modest beta blocker doses, but little additional reductions with high doses.  My approach is to address both rest and exercise heart rates by using the combination of digoxin and a low/moderate dose beta blocker.

Digoxin is even more useful in Aflutter.  Aflutter often occurs in patients with lung disease, where beta blockers can increase airway resistance.  But Aflutter is especially difficult to control with beta blockers alone.  Digoxin really helps.  Remember that you have to give a full loading dose of digoxin to see an effect.  Non-loading doses won’t affect the rate for days.  Also, remember that kidney function does not alter the loading dose but does alter the replacement dose or daily dose.

I have written more extensively about all of this in the past on this blog (1, 2) and elsewhere (3).  The “elsewhere” was in response to the The Rate Control Therapy Evaluation in Permanent Atrial Fibrillation Trial (RATE–AF) (4).  This  was an open-label, endpoint-blinded study (published in JAMA) in which 160 patients, age 60, with permanent Afib were assigned to digoxin or bisoprolol.  All had New York Heart Association Class II heart failure.

Quality of life (QOL) was the primary endpoint.  QOL was not different at 6 months, but more digoxin-treated patients improved their European Heart Rhythm Association symptom classification score 2 classes (53 vs 9%, P <.001).  Serious adverse events occurred in 37 of the bisoprolol and 15 of the digoxin patients. Resting heart rates did not differ.  The point is that the digoxin patients were not dying like flies and seemed to have fewer symptoms and side-effects than the bisoprolol group.

I think that many inexpensive, useful drugs get abandoned because there is no industry push to use them. None of the Afib guidelines list digoxin as first-line therapy because there are no true randomized controlled clinical trials of digoxin, (5) but absence of proof of effectiveness doesn’t equal proof of absence of effectiveness, if it hasn’t been studied.

1.     https://pauldthompsonmd.substack.com/p/digoxin-239-years-and-still-not-certain

2.     https://pauldthompsonmd.substack.com/p/digoxin-try-it-you-might-like-it

3.     https://www.hcplive.com/view/is-digoxin-back-from-the-dead-

4.     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. JAMA. 2020 Dec 22;324(24):2508.

5.     Curfman G. Digitalis Glycosides for Heart Rate Control in Atrial Fibrillation. JAMA. 2020 Dec 22;324(24):2508.

#digoxin #cardiology #atrialfibrillation #atrialflutter #cardiacmedications