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Words Of Wisdom by Prof B. M. Hegde
Has The Curtain Finally Fallen ?
William Withering introduced the foxglove decoction to medicine in the treatment of dropsy more than 200 years ago, thereby ushering in a new era in the therapy of heart failure. In the last two hundred years this drug must have been given to millions of people. Many small studies in the past looked at various aspects of this drug and never before has any other drug been subjected to more audit than digoxin. I reviewed the state of the art of digoxin use way back in 1988.(1) Since then many new studies did come to fruitition and I think it is time to review the subject again. Finally the much awaited extensive, placebo-controlled study of digoxin’s usefulness in heart failure, Digoxin Investigation Group (DIG) has been published (2).
Heart failure is still an enigma and it is very difficult to say how many people die of heart failure and how many die with it. So most of the statistics on death in patients with heart failure have to be taken with a pinch of salt. One has to take into account the accompanying factors before deciding on the management of heart failure. Now that ACE inhibitors (angiotensin-converting-enzyme-inhibitors ) have been shown to reduce death in heart failure patients (3) the need for digoxin is not that urgent as in the past without any specific treatment available.
Positive ionotrophic drugs like digoxin did not find favour in the long run. The drug in question is milrinone, which did more harm than good.(4) Almost similar was the story of vasodilators which came with a bang in the seventies but very soon faded away because of the tachyphylaxis. (5) Earlier studies by Katz and his group did show extra fibrosis in the heart muscle in those patients who died of heart failure treated with digoxin.(6) Tired and ischaemic myocardium finds it difficult to respond to positive ionotrophic drugs. Search for newer ways of treating heart failure brought the new ACE inhibitors into the picture. There have been renewed interest in betablockers in the treatment of heart failure not only of the predominantly diastolic pump dysfunction, but also the global dysfunction variety. CIBIS, using the new betablocker bisaprolol, is one such study.(7)
DIG study referred to above did throw light on some of the important aspects of heart failure management. There were two wings to the trial. The main part of the study looked at patients with severe failure ( left ventricular ejection fractions less than 45% ) and there were 3397 patients in the digoxin group as against 3403 patients in the placebo group. In addition all these patients did receive diuretics, ACE inhibitors and other measures as and when needed. In an anciliary trial there were patients with ejection fractions above 45% ( 492 in the digoxin group and 496 in the placebo group ): in both the groups the patients were randomly allocated to the treatment groups. This was a double blind, placebo controlled, randomised trial in the true sense.
The salient features of the results are as follows:
- Digoxin had no effect on the overall mortality when it was added to diuretics and ACE inhibitors.
- There were fewer deaths due to worsening of the heart failure in the digoxin group.
- Digoxin, unlike other positive ionotrophic agents like dobutamine,beta-agonists, milrinone, enoximone, did not show increased mortality in heart failure.
- Digoxin, however, did show some reduction in the hospitalisation rates in patients with heart failure.
There were more number of people with suspected digoxin toxicity in the group taking the drug but none of them needed hospitalisation because of that and most of their serum digoxin levels were within normal limits on review.
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