Digoxin - Hans ..why avoid it?

I have read Hans recent post ..."drug from hell" ...which references in the footnote a study which I could not locate ...but I get the impression the gist of it was that Digoxin for Lone AF is bad. Can someone summarize the concerns with Digoxin...is the bottom line that it likely makes paroismly AF progress to perminant AF? I'm under the impression that my EP perscribed this rate controll drug as it has the least amount of complications of those out there. I am on .25mg Digoxin once/day and 100 mg Flecenaide twice a day. My afib seems to be in check on the meds until each evening about an hour before my pm dose of Flecanaide, then I get irregular beats (afib/other) until I fall asleep 3-4 hrs later, then wake in NSR.

Looking for others thoughts/comments:

1) Why is Digoxin any worse that other rate control drugs for Lone Afib?
2) What alternative rate control drugs can I ask my EP about?
3) Might I need to increase my Flecanide dose to 150 mg twice a day or take 100 mg three times a day to prevent evening break through?
4) What specific issues have been documented related to long term Flecanide use (ie 10, 20 yrs)?

Well this is a very thin answer at best.

I was on Digoxin for a short period of time after an emergency room visit..

I was told the drug helps the heart beat at a slow stronger rate when needed during afibs.. I was also on Solatol at the same time. I have since dincontined the Digoxin... with no missing of the drug what so ever.
Nor did I feel any benefits from the drug.

I understand this drug is usually prescribed for heart failure patients.

Hi Guy,

Regarding dig and LAF, you may find the below articles titillating.

The atrial arrhythmia syndrome of vagal origin
[www.ncbi.nlm.nih.gov]

Effects of digoxin on acute, atrial fibrillation-induced changes in atrial refractoriness
[www.ncbi.nlm.nih.gov]

Digoxin and membrane sodium potassium ATPase inhibition in cardiovascular disease
[www.ncbi.nlm.nih.gov]

PC

Hi PC,
I found the first link interesting, but the report is 29 years old. Some progress must have been done during that time. The authors write:"and suggests a re-entry mechanism rather than hyper-excitability". Is that really true? Does not the success of recent years PVI-ablations suggests something else? Some physicians ablate a little more than just the PVI, but still the success rate of just PVI ablations suggests something else: "ectopic foci" in the area of the PV sure must play a roll even for vagal affibbers IMO.

PC - thanks for these references. The last clearly spells out why dig would not be the drug of choice. Certainly anything that inhibits the Na/K pump activity (and the prolonging of the refractory period) along with lowering of IC magnesium and increase of IC calcium for more cellular excitability would not be useful.

Here's an opinion:

Digoxin (digitalis glycosides) has a long and chequered history, but the great wheel has again swung against it. A lot of the chronic effect of digoxin may be related to increased vagal tone! Disadvantages however include the low therapeutic index, high incidence of proarrhythmia, and the fact that it maintains atrial fibrillation rather than converting it to sinus rhythm (which is generally now considered far more desirable). Even where digoxin is used for rate control in AF, the rate often goes crazy once the person exercises!

[www.anaesthetist.com]

Hi Gunnar,

I included the first reference, because it was written by Coumel, who was the first to describe VMAF. Even 30 years ago he knew that dig was not good for VMAF and yet we are still struggling with its inappropriate usage in LAF.

IMHO PVI works for both pathologic and physiologic AF because it disconnects the source of the PACs from the left atrium. The substrate of AF remains, however. That's why I feel blessed to have had a successful one. If I hadn't developed physiologic AF at 50, I would have developed pathologic AF at 70.

PC

Guy,

You may already have received the answer to your query from PC and other posters, but if not, the following article from the March 2002 issue of The AFIB Report (in which I coined the phrase "Medicine from Hell") should hopefully do so.

"Digoxin: The Medicine from Hell?
Digoxin (digitalis, Lanoxin), originally derived form the foxglove plant, has been in use for 200 years as a heart medication. The primary indication for digoxin is in the treatment of heart failure (congestive heart failure) especially if accompanied by atrial fibrillation. From this original application digoxin has expanded into the treatment of atrial fibrillation and lone atrial fibrillation. Most medical textbooks still laud digoxin as an effective drug for heart failure. Does it actually work?

The Digitalis Investigation Group, a large team of American and Canadian researchers released a major report, which presents the findings of a large, randomized, double-blind, placebo-controlled trial of digoxin in the treatment of heart failure patients. The three-year trial involved over 7000 patients with heart failure (left ventricular ejection fraction less than 0.45). The patients were divided randomly into two equal-sized groups with one group receiving 0.250 mg of digoxin per day and the other group receiving a placebo; all patients in both groups continued on ACE inhibitors and diuretics. The average follow-up time was 37 months. At the end of the trial 35% of the participants had died in each group. The death rate attributable to worsening heart failure was slightly less in the digoxin group, but the number of deaths from other cardiovascular events such as arrhythmias and strokes was higher. Patients on digoxin were less likely to be admitted to hospital for worsening heart failure (26.8 versus 34.7% for controls), but had higher admission rates for suspected digoxin toxicity (2.0 versus 0.9%).

The researchers conclude that digoxin does not reduce the risk of death from heart failure or other causes, but that it does reduce the rate of hospital admissions, especially for worsening heart failure. In other words, while digoxin may, to some extent, ameliorate the symptoms of heart failure it does not reverse or cure it nor does it reduce the risk of death from this condition[1,2].

British researchers followed 484 heart failure patients for three years and found that the mortality among those taking digoxin was 38.9% as compared to only 21.3% among controls. The researchers conclude that the use of digoxin in heart failure patients is associated with an adverse prognosis and suggest that beta-blockers and spironolactone may be a better choice for ameliorating the symptoms of heart failure[3].

Toxicity and Interactions
The "therapeutic window" for digoxin is very narrow. Most patients are started on a daily dosage of 0.250 mg/day; however, this is often too little for some patients and too much for others. Very careful evaluation is required in order to find just the right dosage. Unfortunately, this is rarely done in actual practice.

Researchers at the Health Care Department in Maryland found that in the period 1985 through 1991 over 200,000 of 3.3 million digitalis users were hospitalised because of digitalis intoxication. It is ironic that digitalis is often prescribed for people who suffer from atrial fibrillation and yet, the most common manifestation of digitalis intoxication is also atrial fibrillation. Other symptoms of digitalis poisoning are nausea, vomiting, diarrhea, psychoses, and fatigue. Perhaps the most disturbing finding in the study is that in 73% of all cases the reason for prescribing the digitalis in the first place was unclear or weak. The researchers also point out that the high level of hospitalisation for adverse effects of digitalis is, to a large extent, due to inadequate monitoring of patients taking the drug. It is also of concern that for the period in which the researchers uncovered data for the 200,000 hospitalizations only 577 adverse events involving digitalis were reported directly to the FDA by doctors or hospitals[4].

Other researchers have noted that digoxin is often prescribed seemingly for no good reason. Dr. Wilbert Aronow of the Mount Sinai School of Medicine found that 19% of patients admitted to a nursing home had been prescribed digoxin. A thorough medical examination and evaluation concluded that 47% of these patients should not be taking digoxin at all. Dr. Aronow also noted that 18% of the patients receiving digoxin had been misdiagnosed as having congestive heart failure when, in fact, they were suffering from edema or dyspnea (laboured breathing). Digoxin therapy was safely discontinued in the 47% of the patients for whom it had been inappropriately prescribed.[5].

Not only is digoxin highly toxic, but it can also interact with herbs such as Siberian ginseng and with antiarrhythmic medications such as flecainide (Tambocor), propafenone (Rythmol), and amiodarone (Cordarone)[6-8]. These drugs all increase blood levels of digoxin thus making a toxic reaction even more likely unless digoxin dosage is adjusted[7,8].

Digoxin and Atrial Fibrillation
Digoxin is still routinely prescribed for patients with atrial fibrillation even though there is no evidence that it is beneficial and growing evidence that it may actually be harmful. Digoxin does not convert atrial fibrillation to sinus rhythm[8,9]. Its ability to slow the heart rate during an atrial fibrillation episode is doubtful[10] and there is no evidence that it prevents future episodes of paroxysmal atrial fibrillation[11,12]. Dr. Rodney Falk, MD of the Boston School of Medicine sums it up, "Digoxin is probably not of value for preventing tachycardia (rapid heart beat) at the onset of paroxysmal atrial fibrillation and its use as sole agent for this indication, although widespread, has no basis"[11].

Not only is digoxin useless in the prevention and treatment of atrial fibrillation it can actually be detrimental. Dr. Philippe Coumel, MD head of the cardiology section of the Hopital Lariboisiere in Paris says, "Not only are beta-blockers or digoxin not indicated in vagal atrial fibrillation, but they are definitely contraindicated as they tend to promote the arrhythmia and may block the action of conventional antiarrhythmic treatment"[13]. Dr. Coumel's statement has been endorsed by the American Heart Association[14].

Researchers at the University of Michigan Medical Center go even further in their condemnation of digoxin. Their conclusion from a recent clinical trial, "The results of the present study suggest that digoxin may facilitate or promote early recurrences of atrial fibrillation after conversion to sinus rhythm not only in patients with vagotonic (vagal) atrial fibrillation, but also among the general population of patients with atrial fibrillation"[15]. It is now also clear that digoxin may not only prolong the duration of episodes, but may actually convert the paroxysmal (intermittent) form to the chronic form[16].

As if this is not enough, researchers have also found that digoxin can cause visual problems even at dosages normally considered safe and may significantly aggravate asthma symptoms[17,18].

Yes, digoxin may truly be the medicine from hell and it certainly should never be used by people with lone atrial fibrillation. If a medicine is needed for the control of heart rate then calcium channel blockers such as verapamil or diltiazem or beta-blockers like atenolol or metoprolol would be a better choice – except for vagal afibbers who should not take beta-blockers.


References
1. Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. New England Journal of Medicine, Vol. 336, No. 8, February 20, 1997, pp. 525-33
2. Packer, Milton. End of the oldest controversy in medicine: are we ready to conclude the debate on digitalis? New England Journal of Medicine, Vol. 336, No. 8, February 20, 1997, pp. 575-76 (editorial)
3. Lindsay, S.J., et al. Digoxin and mortality in chronic heart failure. The Lancet, Vol. 354, September 18, 1999, p. 1003 (research letter)
4. Warren, Joan L., et al. Hospitalizations with adverse events caused by digitalis therapy among elderly Medicare beneficiaries. Archives of Internal Medicine, Vol. 154, July 11, 1994, pp. 1482-87
5. Aronow, Wilbert S. Prevalence of appropriate and inappropriate indications for use of digoxin in older patients at the time of admission to a nursing home. Journal of the American Geriatrics Society, Vol. 44, May 1996, pp. 588-90
6. Fugh-Berman, Adriane. Herb-drug interactions. The Lancet, Vol. 355, January 8, 2000, pp. 134-38
7. Canadian Pharmacists Association. CPS Compendium of Pharmaceuticals and Specialities, 35th edition, 2000, pp. 363, 1409, 1540
8. Podrid, Philip J. and Fuchs, Therese. Oral Antiarrhythmic drugs used for atrial fibrillation. In Atrial Fibrillation: Mechanisms and Management, edited by Rodney H. Falk and Philip J. Podrid, Lippincott-Raven Publishers, Philadelphia, 2nd edition, 1997, pp. 329-69
9. Falk, Rodney H. Atrial fibrillation. New England Journal of Medicine, Vol. 344, No. 14, April 5, 2001, pp. 1067-78
10. Pritchett, Edward L.C. Management of atrial fibrillation. New England Journal of Medicine, Vol. 326, No. 19, May 7, 1992, pp. 1264-71
11. Falk, Rodney, H. Pharmacologic control of the ventricular rate in atrial fibrillation. In Atrial Fibrillation: Mechanisms and Management, edited by Rodney H. Falk and Philip J. Podrid, Lippincott-Raven Publishers, Philadelphia, 2nd edition, 1997, p. 314
12. Miller, Marlene, et al. Efficacy of agents for pharmacologic conversion of atrial fibrillation and subsequent maintenance of sinus rhythm: a meta-analysis of clinical trials. Journal of Family Practice, Vol. 49, November 2000, pp. 1033-46
13. Coumel, Philippe. Paroxysmal atrial fibrillation: a disorder of autonomic tone? European Heart Journal, Vol. 15, suppl A, April 1994, pp. 9-16
14. Prystowsky, Eric N. Management of patients with atrial fibrillation: a statement for healthcare professionals from the subcommittee on electrocardiography and electrophysiology, American Heart Association. Circulation, Vol. 93, March 15, 1996, pp. 1262-77
15. Sticherling, Christian, et al. Effects of digoxin on acute, atrial fibrillation-induced changes in atrial refractoriness. Circulation, Vol. 102, November 14, 2000, pp. 2503-08
16. Falk, Rodney H. Proarrhythmic responses to atrial antiarrhythmic therapy. In Atrial Fibrillation: Mechanisms and Management, edited by Rodney H. Falk and Philip J. Podrid, Lippincott-Raven Publishers, Philadelphia, 2nd edition, 1997, p. 386
17. Butler, Vincent P., et al. Digitalis-induced visual disturbances with therapeutic serum digitalis concentrations. Annals of Internal Medicine, Vol. 123, No. 9, November 1, 1995, pp. 676-80
18. Ayson, Mark, et al. A pilot study to investigate the pulmonary effects of digoxin in patients with asthma. New Zealand Medical Journal, Vol. 108, February 9, 1996, pp. 36-7

Great post, Hans, thank you.
PeggyM