Digoxin tied to increased risk of death in patients with atrial fibrillation

A longtime remedy to treat heart problems is now linked with a higher risk of death for those diagnosed with atrial fibrillation, a new study shows.

- By Becky Bach

Mintu Turakhia has a new study showing that patients with a heart condition known as atrial fibrillation have a higher risk of death from the drug digoxin.
Norbert von der Groeben

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

Foxglove, a genus of flowering plants, contains cardiac glycosides, which can be used to treat heart failure and atrial fibrillation — a rapid and irregular heart rhythm. Now, more than 200 years later, researchers at the School of Medicine have validated Withering’s warning with the discovery that patients with atrial fibrillation who are treated with digoxin, a glycoside commonly extracted from woolly foxglove, are more likely to die than similar patients who received different treatments.

“The take-home point is to question whether people should really be on this drug,” said the study’s 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. “These data challenge the current guidelines.”

The study was published online Aug. 11 in the Journal of the American College of Cardiology, and will appear in the Aug. 19 print issue of the journal.

Turakhia and his team 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. Patients treated with digoxin were 1.2 times 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.

Digoxin can be extracted from woolly foxglove.
Pauline Rosenberg

“This is going to be as close to proof positive as we get because we may never have a randomized trial of this drug,” Turakhia said. Pharmaceutical companies lack the incentive to finance studies on a long-accepted, generic drug.

Evidence gap

Although recent studies showed mixed results, doctors and patients trusted digoxin because of its historic status, Turakhia said.

“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. “

Other Stanford co-authors are Wolfgang Winkelmayer, MD, ScD, associate professor of nephrology; Susan Frayne, MD, professor of medicine; Ciaran Phibbs, PhD, associate professor of pediatrics; and Paul Heidenreich, MD, professor of cardiovascular medicine.

Researchers at the VA-Palo Alto, University of Pennsylvania, the Veterans Affairs Eastern Colorado Health Care System and the University of Colorado-Denver also contributed to the study.

This study was funded by a Veterans Health Services Research and Development Career Development Award, an American Heart Association National Scientist Development grant, a VA Health Services and Development MERIT Award, the National Institute for Diabetes and Digestive and Kidney Disease (grant 1R01DK095024) and the Center for Health Care Evaluation/Center for Innovation to Implementation.

Winkelmeyer is a member of the event adjudication committee for Medtronic, the data safety monitoring board for Medgenics and the scientific advisory boards of Amgen, Bayer, GlaxoSmithKline, Keryx, Mitsubishi-Tanabe and Rockwell.

Information about Stanford’s Department of Medicine, which also supported the work, is available at http://medicine.stanford.edu.

About Stanford Medicine

Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit med.stanford.edu.

2023 ISSUE 1

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