DIGOXIN, DIGOXIN, HOW SAFE ART THOU?

Eversince I was a medical student, digoxin has been with us. This extract from the foxgrove plant has served many a cardiac patient with heart failure. However with newer and better agents for heart failure control and improve survival, my heart failure patients have moved away from digoxin, onto ACE-I and ARBs. However, many of my patients with chronic atrial fibrillation are still on digoxin for rate control. By the way, it is also cheap, and affordable.
So this latest study in the European Heart Journal, Nov 28th online, is rather worrying.
Dr Samy Claude Elayi, and colleagues from the University of Kentucky, USA was part of the AFFIRM ( Atrial fibrillation follow-up investigation for rhythm management trial), followed up the AFFIRM patient for 5 years and compared the outcomes of thos on digoxin with those not on digoxin. This is obviously a sub-study from the main AFFIRM trial. This cohort consist of 4.060 patients with chronic atrial fibrillation. After 5 years of follow-up, they found that those on digoxin had a 41% increase in all cause mortality. There was a 35% increase in cardiac mortality and 61% increase in arrhythmic deaths. Now this is alarming. Broken down in common terms, after 5 years, 1:5 patients with AF given digoxin will die from any cause, 1:8 will die from CVS causes, and 1:16 will die from an arrhythmia. This is alarming.
It is true that when digoxin came to us, centuries ago, there were no large safety trials. We know that digoxin did not improve mortality in patients with heart failure, but did improve symptoms. All the digoxin safety trials, were on heart failure in patients in sinus rhythm. There were no signs of increase deaths here.
This findings by Dr Samy and colleagues obviously needs further larger studies, perhaps, as digoxin i our good old faithful. The authors are not sure of the mechanism for the increase mortality. Neither am I. We certainly have to be more careful and see if any other investigators will substantiate this findings.
Personally, I dare say that I have many patients with AF, on digoxin for 5 years or more. They are still with me on follow-up.
Disturbing, must watch and see.