Digoxin – Is it safe?

Posted by Mike in News

Posted on Tuesday, May 19th, 2015 at 8:00 am

The Daily Mail has, as ever, put a publication onto the public arena which is capable of causing concern (4th May 2015). This is based on a publication in the European Heart Journal of a meta-analysis of studies looking at mortality and use of Digoxin. This appears to show that Digoxin increases mortality by 20%.

To understand why this is probably not true requires an understating of how medical evidence is gathered. The first step is usually observational, where populations are observed over time and various characteristics, lifestyle choices etc are found to be associated with bad outcomes.

To prove that the outcomes have been caused by the drug or lifestyle, it is often necessary to perform a randomised study. This involves the intervention being proscribed by chance rather than an active choice of the patient or physician. This methodology is the randomised control trial or RCT, and this trumps all other trial evidence.

There is only one randomised trial of Digoxin, the DIG trial, which in patients with heart failure there was no effect on mortality but an improvement in hospital admissions (N Engl J Med. 1997 vol. 336 pg. 525-33).

This trial and the RACE II trial (which was randomised in part and showed a benefit in mortality from Digoxin) actually used a higher dose of Digoxin than other trials, making it unlikely that over-dosage of digoxin is the cause of the excess mortality.

The likely explanation of this effect is that Digoxin is given to sicker patients who cannot tolerate other drugs, and therefore in a non-randomised trial appears to be dangerous.

In conclusion, based on the gold standard of RCTS, there is only one trial to look at which was large and showed no excess risk of death where digoxin was given in a randomised fashion.