One of the greatest and most dangerous naturalistic fallacies is that if our ancestors used something, it must be as good or even better than modern science.

In An Account of the Foxglove and Some of its Medical Uses, published in 1785, Sir William Withering cautioned readers that extracts from the plant foxglove, also called digitalis, was not a perfect drug. "Time will fix the real value upon this discovery," he wrote.  

Almost 230 years later, researchers at the Stanford University School of Medicine have validated Withering's warning with the discovery that patients with atrial fibrillation — a rapid and irregular heart rhythm — who are treated with the digitalis-derivative digoxin are more likely to die than similar patients who received different treatments.


Digoxin is extracted from the foxglove plant.
Credit: Don Henise


Other recent studies have also showed mixed results, but doctors and patients have trusted digoxin because of its historical status.  Pharmaceutical companies won't spend tens of millions of dollars to finance studies of a long-accepted, generic drug and the National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health is too busy wasting taxpayer money on quackery.

Lead author Mintu Turakhia, MD, assistant professor of cardiology at Stanford and director of cardiac electrophysiology at the Veterans Affairs Palo Alto Health Care System, and colleagues analyzed records from 122,465 patients who received a new diagnosis of atrial fibrillation from the U.S. Department of Veterans Affairs health-care system between 2003 and 2008. Doctors prescribed digoxin to 23 percent of the patients, and 70 percent of those patients were still on the drug one year later.

They found that patients treated with digoxin were 20 percent more likely to die than comparable patients prescribed other therapies. Patients receiving digoxin were more likely to die regardless of age; use of other drugs such as beta-blockers, amiodarone or warfarin; or the presence of other factors such as kidney disease, heart attack or heart failure, the study found.

 "The take-home point is to question whether people should really be on this drug," said Turakhia. "These data challenge the current guidelines. This is going to be as close to proof positive as we get because we may never have a randomized trial of this drug.

"There's an evidence gap," he said, adding that he launched the investigation because digoxin hasn't been rigorously tested like the many other atrial fibrillation treatment options.

The VA patient pool was predominantly male — only 1,980, or 1.6 percent, were female — and Turakhia has called for additional studies to establish whether the results are applicable to women as well.

Turakhia said many other drugs with better safety results are available to treat atrial fibrillation. Digoxin slows the heart rate but does not correct it to a normal rhythm. "We are not asserting this drug should never be used," he said. "However, in light of the many other drugs that can be used to slow down the heart rate in atrial fibrillation, patients and providers need to ask whether digoxin should be the treatment of choice when there are other, safer drugs. "


Citation: Mintu P. Turakhia, MD, MAS, Pasquale Santangeli, MD, Wolfgang C. Winkelmayer, MD, MPH, ScD, Xiangyan Xu, MS, Aditya J. Ullal, BA, Claire T. Than, MPH, Susan Schmitt, PhD, Tyson H. Holmes, PhD, Susan M. Frayne, MD, MPH, Ciaran S. Phibbs, PhD, Felix Yang, MD, Donald D. Hoang, BA, P. Michael Ho, MD, PhD and Paul A. Heidenreich, MD, MS, 'Increased Mortality Associated With Digoxin in Contemporary Patients With Atrial Fibrillation: Findings From the TREAT-AF Study',  Journal of the American College of Cardiology,  2014;64(7):660-668. doi:10.1016/j.jacc.2014.03.060. Source: Stanford University Medical Center