GW Researchers Find Stopping Digoxin is Linked to Poor Outcomes in Some Heart Failure Patients

WASHINGTON (July 30, 2019) — Clinician researchers with the Washington DC VA Medical Center published an original research paper to be printed in the August 5, 2019 issue of the Journal of the American College of Cardiology. The study shows that stopping digoxin in some patients with heart failure is linked to higher risk of death and hospital readmission. Digoxin reduces the risk of hospital admission and readmission in patients with more severe heart failure – those with left ventricular ejection fraction 45% or lower. Left ventricular ejection fraction is a measure of the pumping ability of the heart’s main chamber – also known as the left ventricle – and values 50% or higher are considered normal.

“Findings from our study show that hospitalized patients with heart failure and reduced ejection fraction, who were receiving digoxin before hospitalization, were more likely to die or be re-hospitalized if their digoxin therapy was stopped than if digoxin was continued,” said Awais Malik, MD, a medical resident of the Washington DC VA Medical Center and Georgetown University Internal Medicine Residency Program. “These results are important as the vast majority of these patients were receiving ACE inhibitors and beta-blockers – drugs that are recommended by heart failure guidelines, and yet stopping digoxin increased the risk for poor outcomes.”

Another Washington DC VA Medical Center study published in the American Journal of Medicine, May 29, 2019,  suggests that when hospitalized patients with heart failure and ejection fraction 45% or lower are newly started on digoxin, they are less likely to be readmitted than those discharged without digoxin. The vast majority of the patients in that study were also receiving ACE inhibitors and beta-blockers.

“The issue of being on ACE inhibitors and beta-blockers is important for patients with heart failure and reduced ejection fraction as there is solid evidence that these drugs reduce the risk of both death and hospitalization. Digoxin initiation, in contrast, only reduces the risk of hospitalization and has no effect on death. Thus, if a patient with heart failure is doing well on an ACE inhibitor and a beta-blocker, there may not be a need to initiate therapy with digoxin,” said Steven Singh, MD,  former chief of cardiology of the Washington DC VA Medical Center and professor and assistant dean for education of Georgetown University. “However, findings from our current study suggest that for patients who are already on digoxin, stopping the drug may not be a good idea.” 

“Over 60% of the patients in our study were receiving ACE inhibitors and beta-blockers, and yet 54% of the patients   returned to the hospital within six months of discharge, and this rate went up to 59% if digoxin was stopped. The rate of readmission due to worsening heart failure went up from 29% to 35% if digoxin was stopped,” said Ali Ahmed, MD, MPH, associate chief of staff for health and aging of the Washington DC VA Medical Center and professor of medicine at the George Washington University and Georgetown University and the study’s senior investigator.

Furthermore, Ahmed explains, “These findings that stopping digoxin is bad, taken together with the findings from our other study that starting digoxin maybe good, and the fact that digoxin is relatively inexpensive and safe, suggest that digoxin may still play a role in today’s patients with heart failure and reduced ejection fraction”.

Heart failure is a leading cause for hospital admission and readmission among older Americans. In the DIG (Digitalis Investigation Group) trial, the largest randomized controlled trial of digoxin in heart failure, digoxin reduced the risk of all-cause and heart failure hospitalization but had no effect on death. Because other heart failure drugs such as ACE inhibitors and beta-blockers reduce the risk of both death and hospitalization, the use of digoxin has declined in recent years.

Digoxin is approved by the U.S. Food and Drug Administration to reduce the risk of hospitalizations due to worsening heart failure and the American College of Cardiology Foundation/American Heart Association heart failure guidelines recommend its use for that purpose in patients with heart failure with reduced ejection fraction.

“The study highlights an issue that is important for Veterans as heart failure is a leading cause for hospital readmission in the VA health care system. Future research is planned to further study this issue in Veterans with heart failure using VA’s national database and innovative advanced machine learning techniques,” said Charles Faselis, MD, chief of staff at the Washington DC VA Medical Center and professor of medicine at George Washington University. “The two lead authors of the study are medical residents, which highlights the important role the DC VA Medical Center is playing in fostering academic scholarly activities among academic partner trainees.”

Malik and his colleagues studied 1,396 patients with heart failure with reduced ejection fraction – digoxin therapy was stopped in 698 and was continued in 698. Patients in the two groups were similar on 50 baseline characteristics including ejection fraction and worsening kidney function.

These patients were enrolled in OPTIMIZE-HF – a large national heart failure registry based on 259 hospitals from 48 lower states during 2003 and 2004. The study was funded by GlaxoSmithKline to Gregg Fonarow, MD,  of the University of California, Los Angeles, who is also an investigator in the study. GlaxoSmithKline played no role in the design or analysis of this study.

Other coauthors in the study are Ravi Masson, MD from the Washington DC VA Medical Center, and Georgetown   University, Washington, DC; Wen-Chih Wu, MD from the VA Medical Center, Providence, RI and Brown University, Providence, RI; Milton Packer, MD from the Baylor University Medical Center, Dallas, TX; Bertram Pitt, MD from the University of Michigan, Ann Arbor, MI; Finn Waagstein, MD, PHD from the University of Gothenburg, Gothenburg, Sweden; Charity J. Morgan, PhD from the University of Alabama at Birmingham, Birmingham, AL; and Richard M. Allman, MD from the George Washington University, Washington, DC.

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This release is posted courtesy of the Washington DC Veterans Affairs Medical Center.

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