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Digoxin linked to higher mortality in AF

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Look for alternative digoxin for AF

Digoxin remains a commonly used agent for control of ventricular rate in atrial fibrillation (AF) and is accepted as a valid therapy. Despite endorsement of digoxin in clinical practice guidelines for rate control in atrial fibrillation, there are only limited, conflicting, and mostly older observational data on the safety of digoxin in AF. There have been no appropriately designed clinical trials to assess the safety of digoxin in any patient population. In heart failure cohorts, the effectiveness and safety of digoxin has been shown to vary by serum digoxin concentrations, indicating possible moderation by kidney function.

The meta-analysis of five cohort studies and randomized controlled trials by Dr. Qureshi and colleagues concludes that digoxin is associated with a 27% increased risk of mortality in patients with AF. These results confirm another recently published analysis with similar conclusions, TREAT-AF (J. Am. Coll. Cardiol. 2014;64:660-8).

The TREAT-AF study was a retrospective analysis of patients with newly diagnosed AF. In this study, treatment with digoxin was independently associated with mortality, regardless of age, sex, kidney function, heart failure status, concomitant therapies, or drug adherence. Sensitivity analyses to assess the possible impact of unmeasured confounders make it highly unlikely that any influenced the result of the TREAT-AF Study.

Prospective studies are needed to confirm the findings of these observational reports and to explore the mechanisms responsible for the increased risk of mortality in patients with AF treated with digoxin. In the meantime, physicians should consider alternatives to digoxin in managing patients with AF.

N.A. Mark Estes III, MD, is professor of medicine at Tufts University, Boston. He has no relevant disclosures.




SAN DIEGO – Digoxin increases the risk of death by 27% in patients with atrial fibrillation, a meta-analysis of 19 studies showed.

Patients with AF and kidney failure faced a 60% to 70 % increase in mortality compared to their counterparts not taking digoxin, according to a press release on the study.

A weaker association between digoxin and death was observed in AF patients who also had heart failure, a finding the authors suggest warrants further investigation.

“Until further research can be done, I would suggest physicians use caution when prescribing digoxin for patients with atrial fibrillation, especially given that there are alternative drugs available that might be safer,” lead author Dr. Waqas Qureshi said in a statement.

The results were released in advance of their March 15 presentation at the annual meeting of the American College of Cardiology in San Diego.

About 5.6 million Americans have atrial fibrillation (AF) and roughly 1 in 5 are prescribed digoxin for heart rate control.

Current guidelines recommend digoxin as first-line therapy in patients who aren’t physically active and as a second-line drug for more active patients.

“Based on consistent results coming out of many studies, our results suggest digoxin should be downgraded from its position as a front-line agent for certain patients with atrial fibrillation,” Dr. Qureshi, a clinical and research cardiology fellow at Wake Forest School of Medicine in Winston-Salem, N.C., recommended.

The authors reviewed 19 studies including five cohort and randomized controlled trials involving 501,681 patients. Of these, 458,311 patients had AF and 111,978 were prescribed digoxin.

In a random effects model, digoxin was associated with an increased risk of mortality, with a pooled hazard ratio of 1.27 (95% confidence interval 1.19-1.36; P value < .001).

Several studies in the meta-analysis suggest that higher blood levels of digoxin increase the risk of death. The mechanism behind the increased mortality is not known, although previous studies have suggested digoxin increases the risk of thromboembolism.

The meta-analysis accounted for risk factors and co-morbidities reported in the various studies, but it’s possible that some confounding factors may not have been accounted for, the authors acknowledge.

“The study points to the need for a well-structured, targeted trial to investigate digoxin’s safety,” Dr. Qureshi stated.

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