Breaking the science of Heart failure :
Heart failure (HFrEF) remains a gigantic clinico-pharmacological entity. In the last decade, pharmacological strategies to tame HF turned out to be a multi-billion global block buster. Industry constructed multiple evidence-based pillars to lift the drowning patients from HF. To be precise, there were four (Some wanted to insert a fifth pillar : Riociguat a sensitizer of soluble guanylate cyclase (sGC) which play mimicry with Nitic oxide ). All sounds good and right on paper .
But, what was hidden from the public was, that they were built displacing the foundation on which heart failure was managed for centuries if not decades. Yes, it’s about the foxglove-derived grand old drug Digoxin, a Na+ /K+ATPase blocker in the myocyte cell membrane, that exchanges calcium for stable Inotropy. Digoxin is only positive Inotropic with vago -mimitic action that calms the heart. Though the efficacy to safety margin is low in terms of pro arrhythmia , if used properly Digoxin had been a key drug in HF especially if AF is associated. Over time, we have developed RASS sympathetic blockade system in various forms. One poorly done study in 1990s, DIG-Trail, was enough to paint black on the wonder drug.
Now, In 2025, it seems apparent, lack of that vital foundation might shake the pillars, built with ornamental ARNI’s and the flimsy Flozins (Which are essentially renal glycosuric agents also playing a diuretic role , in the process partly stealing the benefits from time-tested diuretics)
This post was written in this site about long back, questioning the DIG trial conclusion (Click here)
Delighted to note , the observations were ratified today.
Now in 2025, the ESC congress in Madrid, some sensible study group from Germany and France found Digoxin indeed saves lives, confirming the suspicius results of DIG trial results done in 1997.(Which claimed no mortality benafit )
Back to Catch 22 situation
This time, in DIGIT -HF they used Digitoxin instead of Digoxin. Why ? again, something sounds fishy. Digoxin is the true universal generic available for a peanut price. I am not sure about the availability and price of Digitoxin. This trial is is really kick all those modern cardiologists who get humiliated to write this old drug.
Meanwhile, a near foolish argument is already on , questioning Digitoxin cannot be compared with Digoxin as the former is more stable, has a hepatic route to eliminate if HF patients are renally compromised, etc. I checked with the pharma guys. Digitoxin is difficult to get. My fear is someone may patent this new improved German Digitoxin that was used in this study. (Digitoxin -Trade Name Crystodigin)
Final message
It is glad to see Digoxin continue to defy the death sentence passed by modern day scientists. Though DIGIT-HF is a good come back, we need to allow more truths to come out from the secret scientific cupboards.
Dr.S.Venkatesan MD 