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Archive for September, 2019

William Withering the British Botanist of 18th century now laid to rest in the St Barthomlew Churchyard ,Edgbaston is known for his astonishing isolation of the wonder moelcule Digoxin from Foxglove. (Of course, let us not forget original old lady Ms. Hutton from Shropshire who was treating epidemic dropsy with a concoction of herbal Tea ) He reported this in the seminal paper “An account of Foxglove’ in the year 1750 and subsequently became a fellow of Royal college of science.

(The story of Withering and Digoxin is extensively researched and written by Dr Dennis M, Krikler in a classic review article of 1985 JACC )

Near-death experience of Digoxin

After 250 years , saving millions of life, modern science has killed this warrior (inadvertently ?) by a minuscule study with serious flaws called DIG trial *published in NEJM 1997. It exposed the truth that science in flimsy forms can misrepresent fact. Actually many wouldn’t agree its a bad study. But , everyone realised , the conclusion was misinterpreted and disproportionately given weight to one aspect.The conclusion was worded in such a fashion, which sort of implied a negative bias.

*Yes , flaws were discussed in one of our detailed journal club meeting .

DIG trial

This one study was good enough to smear this drug with a knockout punch as if we are administering poison to a patient with heart failure.Thus a grand old drug became an object of ridicule in academic forums. Subsequent offline real-world scrutiny clearly indicated reduced hospital rate admissions and preventing worsening of HF was directly improving the mortality for which there were no takers. At least occasionally we need to realize there is foolish face for statistics. Now we are beginning to restore some lost sense.

 

What’s happening in 2019

The same scientific methodology finds Digoxin to have great value . JACC.  Awais Malik from Veterans Affairs Medical Center, Washington DC and others try to  dig out a truth.

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Whoever is blaming this as a withdrawal study are requested to go through the basics of how adding a drug doesn’t help but stopping it worsens. Another group has a different issue. There is a tendency among the scientific community, to look down on studies done in VA hospitals as if they have lesser academic value. I strongly object to that if it’s true. Never have preformed opinion about a study by its source.

How does Digoxin act?

Mind you, Digoxin was working all alone in CHF in the past without the help of all-powerful loop diuretics which was discovered 200 years later, This adds more credit to Digoxin since it has a combined the action of diuretic, anti sympathetic and vagal modulating action, and AV nodal regulation. The only issue with Digoxin could be its safety profile, which if carefully taken care can be overcome. (Afterall, we are trained for this job ) One may call it a most comprehensive drug amongst others in cardiac failure.

Final message

Ignore the greatness of old drugs at your own peril. Foxglove blossoms again, after a gap of 30 years. Please don’t crush it this time! Let Willaim Withering smile from deep inside his resting place at Barthomlew Church along with millions of heart failure patients.

 

Reference

1.

2.History of William Withering

3.Ahmed A, Rich MW, Love TE, et al. Digoxin and reduction in mortality and hospitalization in heart failure: A comprehensive post hoc analysis of the DIG trial. Eur Heart J. 2006;27(2):178-186

Postamble 

A funny business Idea

I guess Parke Davis those days had wholesome rights for Digoxin. May I suggest few tips for the industry how to capitalise this newly generated enthusiasm. Please ensure this drug sounds anything other than Digoxin which seems to have a stigma attached for the modern guys.

Try renaming this drug , a sodium-potassium ATPase blocker, as DiNaKatban and patent  it as a unique weekly depot Injection with an attractive  499$ price tag. Another option is to add Digoxin ,Neprilysin and Frusemide,  possibly an ARB  ( Dinephrimab) and project it as polypill for HFrEF . Publish it in NEJM with a huge non Inferiority trial,break it in  ESC or ACC .Consider a subscription based service linking it with Netflix or Apple account .Sell it on all heart failure clinics with a special launch. I am sure, the same guys who ridiculed this drug for so long, will ask their patients to stand first in the queue.Call me, if this new generation Digoxin doesn’t vanish like hot cakes from these pharma malls.

 

 

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Preamble

Hey dudes, will you stent this 76 year old  fragile man’s Aortic valve ?  It looks shaggy and it seems to be leaking as well.Iam not sure its really tricuspid or not .It is so distorted . By the way , he also has a left main lesion with no protection.What shall we do ? Will the Jena valve do the trick ? My experienced collegue threw this question to a flock of freshly hatched senior residents of a upscale cardiac center. 

After rapidly feeding the necessary risk predicting numericals, clinical and hybrid imagery data , they dug deep into the iOS-powered gadget, loaded with latest TAVR app fused with SYNTAX 2 and FAME 2 overlay for few minutes and started responding one by one.

Yes sir , no Issues, we can comfortably stent it , Its class 2 A / with level B evidence according to JACC intervention article, but, I must say , it was class 2B just a month ago. Another fellow interfered, no sir, ESC says it’s still class 3 but the evidence is C so I am  not sure how to interpret it. The third fellow who usually is a quiet guy, came up with this, but sir, It seems TCT and EURO-PCR  has just released an update, the indication is currently upgraded to class 1 backed by level A evidence

Are you talking about TAVR or Left main? the confused consultant quipped… that’s EBM at its best !

Evidence-based errors in cardiology 

Evidence is the most sacred word in current medical practice. How much of our practice is evidence-based ? It is considered as a quality check. But, today we harshly understand, the evidence to which our conviction clings has a very short expiry date. Apart from expiry , the evidence thing comes with serious invisible manufacturing  defects as well. It may become null and void  even before its fully disseminated into the patient domain.(Please mind, your patient’s life is tied to this clueless evidence !)

So, how to tackle this dangerous dissemination of premature wrong evidence from injuring the patient ?

We don’t have a definite answer  . . . except to say, use the available evidence carefully and cautiously. If necessary (it will often be) throw it to the nearest dustbin by your own evaluation assisted by intuition, and a liberal dose of learned empiricism. Mind you, to do this you must be blessed with enough knowledge, wisdom, and courage as you need to overcome strong pressure to do the opposite.

My prediction is, bulk of the future problems in medicine would come from failure to dispose evidence based errors in medicine.

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The most premier course in medicine, DM cardiology just got an entry makeover.

The qualifying mark was lowered to 20% from the current 50th percentile The reason is many private medical college seats went vacant after the Initial counselling in NEET superspeciality exams.

Becoming a cardiologist was a dream come true for those days for us. “You have to read the red covered 3rd edition Brunwald and all clinical chapters from Hurst for two full years” before even to think of writing DM entrance, my senior used to tell me in late 1980s.Yes, life may still be tough in post graduate entrance but, there is an exclusive fast lane for privileged few where the “Goal posts”start coming towards you.Thanks to the explosion of private medical institutes.

Nothing wrong, it’s not a medical calamity. If the entry is made easy. It doesn’t mean all students are below par.Just 80 % below par.

One big consolation

Medicine is an art to be learned. Unfortunately (or fortunately) students of medicine requires more of sincerity, hardwork, motivation, honesty and Intention to learn. Intelligence and knowledge is there in the list but definitely not in the top.

While mediocrity is a menace in medical education, three decades into medical profession, my conscience tells me even merit, expertise, competence end up as double edged swords if they land up in wrong place with a dubious motive. So, ultimately academic guarding of all these so called entry and exit points to DM courses doesn’t really matter much.

Get ready for grand future

Let’s welcome all the new generation cardiologists in whatever form and this country needs more of them to tame the raising cardiovascular disease burden.

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