Digoxin may be associated with higher death risk in newly diagnosed afib patients

In a challenge to existing guidelines, a new study has found digoxin is associated with an elevated risk of death in patients with newly diagnosed atrial fibrillation.

For their retrospective cohort study, researchers used data from 122,465 patients with newly diagnosed nonvalvular atrial fibrillation who were treated in the Veterans Affairs health care system between Oct. 1, 2003, and Sept. 30, 2008. All patients had at least 1 outpatient visit within 90 days of the index diagnosis. Researchers compared patients who started taking digoxin during the 90-day window with those who didn't and evaluated time to death. The average age for all patients was 72 years, and 98.4% of patients were men. Results were published online August 11 by the Journal of the American College of Cardiology.

About 23% of patients (n=28,679) received digoxin, and cumulative death rates were higher for these patients than for untreated patients (95 vs. 67 per 1,000 person-years; hazard ratio [HR], 1.37; P<0.001). Fewer than 25% of those given digoxin had been diagnosed with heart failure. Digoxin use was still associated with greater mortality after multivariate analysis (HR, 1.26; P<0.001) and propensity matching (HR, 1.21; P<0.001). The elevated mortality risk with digoxin was independent of age, sex, kidney function, heart failure, drug adherence, or concomitant use of warfarin, amiodarone, or beta-blockers.

Study limitations include that patients were primarily men and that heart failure severity—which could be a source of confounding—was unmeasured. Also, the use of all-cause rather than specific mortality might have stymied insight into how drug exposure could have led to death, the researchers noted. Still, the results present a challenge to some current guidelines that recommend digoxin as an adjunct to rate-control monotherapy, the authors concluded.

An editorialist noted the study had several strengths, including a very large sample size, a contemporary time frame for observation, and patients from many different U.S. centers. However, he noted, the results must be interpreted cautiously since treatment choices aren't random and are usually made on the basis of factors that can't be measured in observational analysis. “It seems likely that digoxin is selectively used in higher-risk patients, and that these and possibly other unmeasured factors could mediate the reported relationship between digoxin and mortality,” he wrote. The upshot, he concluded, was that digoxin should be used selectively and carefully with atrial fibrillation patients and that dosing should be conservative, especially in elderly patients.