Digoxin Tied to Higher Death Rates in Patients with Atrial Fibrillation

By Will Boggs MD

NEW YORK - Although recommended as a treatment for atrial fibrillation/flutter (AF), digoxin use is associated with an increased risk of death in patients who have been newly diagnosed with the condition, researchers have found.

"For first-line therapy, prior to our study, the guidelines had already moved the needle from 'digoxin is probably good' to 'digoxin might or might not be good,'" said Dr. Mintu P. Turakhia from Veterans Affairs Palo Alto Health Care System and Stanford University School of Medicine in California told Reuters Health.

"I think that the results of our study move the needle further to 'probably is not good,' especially in light of so many other safe and effective therapies available for AF," he told Reuters Health by email, noting that between 20% and 40% of AF patients in the U.S. are put on digoxin.

Dr. Turakhia and colleagues in the TREAT-AF study identified 122,465 patients with newly diagnosed, nonvalvular AF and compared the mortality of the 28,679 who received digoxin within 90 days of initial diagnosis with that of the others.

Cumulative death rates were higher among digoxin-treated patients than among untreated patients (95 vs. 67 per 1,000 person-years; p<0.001), the team reports in the August 19 Journal of the American College of Cardiology.

Use of the drug was associated with a significantly increased risk of death both after multivariate adjustment (hazard ratio, 1.26) and in a propensity-matched comparison (HR, 1.21).

The increased risk of death associated with digoxin was present across all strata of kidney function, except dialysis patients, but there was no indication of an effect modification by eGFR group.

The observations were also consistent across subgroups of drug adherence, heart failure, and concomitant therapy with beta-blockers or amiodarone.

"From the patient perspective, the overall or absolute risk difference is small," Dr. Turakhia said. "We were really looking to evaluate safety across the population of a large health care system. Therefore, it's not like this is a ticking time bomb. In fact, patients could cause more harm if they abruptly discontinue the drug without guidance. This is not an urgent issue if you feel well - so speak to your doctor when the time is right."

"I'm also not saying that all patients should stop the drug and all doctors should stop using it," he said. "There may be perfectly valid reasons. However, in light of the many other drugs that can be used to slow down the heart rate in atrial fibrillation (and improved therapies to maintain sinus rhythm), patients and clinicians need to ask whether digoxin should be the treatment of choice when there are other, safer options."

Dr. Matthew R. Reynolds, who wrote an editorial about the findings, said studies have yielded mixed results on the safety of digoxin for rate control in AF.

"Some reports, including this new one, have suggested potential harm," Dr. Reynolds of Lahey Hospital & Medical Center in Burlington, Massachusetts, told Reuters Health. "The data are not conclusive, but given these concerns, digoxin should be used carefully in patients with AF, and only after trying other options. Nonetheless, digoxin remains helpful for some patients."

Dr. Mitesh Shah from McGill University Health Center, Montreal, Quebec, Canada published a similar study of patients in Quebec aged 65 years and older earlier this month.

"Digoxin is indeed harmful in patients with AF," he told Reuters Health by email. "It should be better to avoid digoxin as much as we can. However, in sick patients, such as patients with incidental heart failure (HF), where digoxin could be a drug of choice, we should carefully prescribe this medication and we should regularly follow-up patients."

He also pointed out the possible danger of combining digoxin with amiodarone (though such an association was not seen in the current study). "Clinicians should be cautious about concomitant prescription of digoxin and amiodarone in patients with AF and HF," he said.

SOURCE: https://bit.ly/1lRxOIt

J Am Coll Cardiol 2014;64:660-668, 669-671.

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