SAN FRANCISCO—Digoxin was independently associated with a more than twofold higher rate of death, based on the large, contemporary cohort study, ATRIA-CVRN, of adults with newly diagnosed atrial fibrillation and no history of heart failure, presented March 9 at the American College of Cardiology (ACC) scientific session. Given other available options for heart rate control, the researchers said that the role of digoxin in the management of atrial fibrillation “should be reconsidered.”
Currently, guidelines endorse digoxin (Lanoxin, GlaxoSmithKline) for heart rate control in patients with atrial fibrillation, but “the studies upon which that recommendation was based are limited and have very short follow-up,” the study’s lead author James V. Freeman, MD, MPH, of Stanford University School of Medicine in Stanford, Calif., told Cardiovascular Business.
“We demonstrated some significant safety issues with using digoxin in these patients and a follow-up of approximately one year,” Freeman said.
The researchers identified all adults diagnosed with incident atrial fibrillation between January 2006 and June 2009 within Kaiser Permanente Northern California and Southern California and without a history of heart failure or digoxin use. They used multivariable extended Cox regression to examine the association between newly initiated digoxin use and risk of death and hospitalization, after adjustment for demographic characteristics, comorbidity, selected laboratory results, medications and the propensity to receive digoxin.
Among 23,272 newly diagnosed atrial fibrillation patients, 12.9 percent received digoxin during follow-up. During a median eight months of follow-up, incident digoxin use was associated with a higher rate of death (9.49 vs. 4.27, per 100 person years), but no difference in the rate of hospitalization (3.18 vs. 3.25, per 100 person years).
After adjustment for potential confounders, incident digoxin use was associated with more than two-fold increased risk of death, and no significant difference in the risk of hospitalization. The crude rate of death on vs. off digoxin therapy was 9.49 vs. 4.27 per 100 person years, respectively. However, the crude rate of hospitalization was not significantly different for patients receiving digoxin vs. those off digoxin therapy with 3.18 vs. 3.25 per 100 person years, respectively.
“We were not able to assess the cause of death in most cases, but we do know that most of the mortality incidence occurred out of the hospital,” said Freeman. “Based on these results, it appears that these patients are dying, but not getting hospitalized, which could indicate sudden cardiac death as a cause.” But he stressed that was speculative on his part.
Rate of death results were consistent in analyses stratified by gender (2.03 in men and 2.13 in women) and age (2.31 in 21-74 year-olds, 1.66 in 75-84 year-olds and 2.5 in those 85 years and older), according to the researchers.
“Based on this cohort, we would recommend that there should be a reassessment of the guidelines,” said Freeman. “While digoxin has been decreasingly used in practice, our cohort reveals that 17 percent of patients were newly initiated on digoxin after newly being diagnosed with atrial fibrillation in a relatively short time frame in the Kaiser system. Thus, it is still being used relatively frequently.”