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Digoxin Associated With Higher Risk of Death and Hospitalization in Adults With Atrial Fibrillation and No Heart Failure

November 21, 2014

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OAKLAND, Calif. — Digoxin, a drug commonly used to treat heart conditions, was associated with a 71 percent higher risk of death and a 63 percent higher risk of hospitalization among adults with diagnosed atrial fibrillation and no evidence of heart failure, according to a Kaiser Permanente study that appears in the current online issue of Circulation: Arrhythmia and Electrophysiology.

Digoxin is a drug derived from digitalis, which has been used for more than a century for heart-rate control in patients with atrial fibrillation, and it remains commonly used for this purpose worldwide. Current clinical practice guidelines for the management of atrial fibrillation recommend the use of digoxin alone for resting heart-rate control in sedentary individuals.

“Our findings suggest that the use of digoxin should be re-evaluated for the treatment of atrial fibrillation in contemporary clinical practice,” said study co-author Anthony Steimle, MD, chief of Cardiology at Kaiser Permanente Santa Clara Medical Center. “Given the other options available for heart-rate control, digoxin should be used with caution in the management of atrial fibrillation, especially in the absence of symptomatic systolic heart failure.”

The results of this study follow findings by many of the same investigators in a 2013 study that revealed digoxin was associated with a 72 percent higher rate of death among adults with newly diagnosed systolic heart failure.

The current study was conducted between Jan. 1, 2006 and June 30, 2009 among nearly 15,000 adults within Kaiser Permanente’s Northern and Southern California regions who had recently diagnosed atrial fibrillation and no prior heart failure or digoxin use. Researchers examined the independent association between newly initiated digoxin use and the risks of death and hospitalization.

During the study period, 4,858, or 17.8 percent, of the participants initiated digoxin use. There were 1,140 deaths among the study cohort, with a significantly higher rate of death in digoxin users compared with non-users (8.3 vs. 4.9 per 100 person years). At the same time, there were 8,456 hospitalizations for any cause, and the rate of hospitalization was higher for patients who received digoxin compared with those who did not (60.1 vs. 37.2 per 100 person years).

“Digoxin remains commonly used for rate control in atrial fibrillation, but very limited data exist to support this practice — mostly small, older clinical studies with very limited follow-up that did not assess the long-term effects of digoxin on mortality or hospitalization,” said Alan S. Go, MD, senior author of the study and research scientist at the Kaiser Permanente Division of Research in Oakland, Calif.

“In contrast, this study included the largest and most diverse sample of adults with incident atrial fibrillation not complicated by heart failure treated in clinical practice reported to date, with results that were consistent across age and gender,” said Dr. Go. “We believe these findings, which build on earlier work, have significant value in guiding clinical cardiology decision-making in regard to digoxin use in the modern era.”

Other authors on the study include James V. Freeman, MD, MPH, Yale University School of Medicine; Kristi Reynolds, PhD, and Teresa N. Harrison, SM, Department of Research and Evaluation, Kaiser Permanente Southern California; Margaret Fang, MD, MPH, University of California, San Francisco; Natalia Udaltsova, PhD, and Niela K. Pomernacki, BA, Division of Research, Kaiser Permanente Northern California; Leila H. Borowsky, MPH, Massachusetts General Hospital; and Daniel E. Singer, MD, Harvard Medical School.

The study was supported by the National Heart, Lung and Blood Institute and the National Institutes of Health [RC2 HL101589 and U19 HL91179], and the American Heart Association Pharmaceutical Roundtable-Spina Cardiovascular Outcomes Research Center program [0875162N].

About the Kaiser Permanente Division of Research
The Kaiser Permanente Division of Research conducts, publishes and disseminates epidemiologic and health services research to improve the health and medical care of Kaiser Permanente members and the society at large. It seeks to understand the determinants of illness and well-being and to improve the quality and cost-effectiveness of health care. Currently, the Division’s 550+ staff are working on more than 350 ongoing research studies in behavioral health and aging, cancer, cardiovascular and metabolic conditions, health care delivery and policy, infectious diseases, vaccine safety and effectiveness, and women’s and children’s health.

About Kaiser Permanente
Kaiser Permanente is committed to helping shape the future of health care. We are recognized as one of America’s leading health care providers and not-for-profit health plans. Founded in 1945, our mission is to provide high-quality, affordable health care services and to improve the health of our members and the communities we serve. We currently serve approximately 9.5 million members in eight states and the District of Columbia. Care for members and patients is focused on their total health and guided by their personal physicians, specialists and team of caregivers. Our expert and caring medical teams are empowered and supported by industry-leading technology advances and tools for health promotion, disease prevention, state-of-the-art care delivery and world-class chronic disease management. Kaiser Permanente is dedicated to care innovations, clinical research, health education and the support of community health. For more information, go to: