Low-dose digoxin saves on side effects
No increased benefits to high doses
A recent study on digoxin (Glaxo Wellcome’s Lanoxin) could have important cost-cutting benefits for cardiac care units (CCU) because it showed that patients with moderate heart failure derive similar benefits from low and moderate doses of digoxin.1
Reduced medical costs are not a result of the lower cost of the lower dosage. The cost of digoxin is not a factor because it costs only about $27.52 per year. The cost savings is derived from reduced hospitalization because of avoided side effects.
Administering low-dose digoxin in the CCU could reduce the numbers of hospitalizations and even some deaths caused by side effects of higher doses, and patients still would see the same positive outcomes, says Eric J. Eichhorn, MD, FACC, a co-author of the study, associate professor of medicine at the University of Texas Southwestern Medical Center in Dallas, and the director of the cardiac catheterization laboratory at the Dallas Veterans Administration Hospital.
"We found the majority of the benefit of digoxin seems to be at a low dose with no additional benefit at a higher dose," Eichhorn says. "At the higher dose you get toxicity and no additional beneficial effects, so this would serve to suggest to clinicians that we should probably use lower doses."
When patients receive digoxin in doses higher than 0.25 mg/day, they may be predisposed to arrhythmias and sudden death. Lower doses do not carry the same risks. "Digoxin’s beneficial effects are improved hemodynamics and exercise tolerance," Eichhorn says.
Mechanism ultimately harms the heart
Digoxin reduces the sympathetic discharge of the heart. When the heart begins to fail, several compensatory mechanisms improve hemodynamics. But over time, the neurohormones tend to harm the heart. "This causes a progressive downhill course for people with heart failure," Eichhorn explains.
Over a two-week period, some study participants with moderate heart failure and a left ventricular ejection fraction of less than 0.45 were given a low digoxin dose 0.125 mg/day and some were given a moderate dose 0.25 mg/day. All but one patient received a constant dose of angiotensin-converting enzyme inhibitor throughout the study; that patient received hydralazine and isosorbide dinitrate.
The study found that the low dose digoxin increased ventricular performance significantly, but the moderate dose had no further increase in performance. The low dose reduced heart rate and increased heart rate variability. Also, neither dose increased parasympathetic activity.
While digoxin’s beneficial effects have been understood only in recent years, the drug has been in use for more than 200 years. However, until this study, researchers and cardiac physicians were unclear about the dosage that would be most beneficial to heart patients.
"Some studies from 30 years ago were done with less than sophisticated methodology, and they came to different conclusions," Eichhorn says. "I was curious about whether there was an additional benefit to a higher dose. I assumed when I started the study there would be, and I was amazed there wasn’t."
An earlier study by the Digitalis Investigation Group as well as a recent report from the National Heart, Lung, and Blood Institute (NHLBI) show that giving digoxin to heart patients helps keep them out of the hospital.2 Nearly 8,000 patients who had sinus rhythm with a diagnosis of heart failure were randomly assigned to receive digoxin or a placebo and followed for three to five years. Twenty-seven percent of the patients on digoxin were hospitalized specifically for heart failure, compared with 35% of the placebo group. The Digitalis Investigation Group found no effect on survival.
(Editor’s note: The NHLBI report can be accessed on the Internet at http://www.nih.gov/news/ pr/feb97/nhlbi-19.htm.)
References
1. Slatton ML, Irani WN, Hall, SA, et al. Does digoxin provide additional hemodynamic and autonomic benefit at higher doses in patients with mild to moderate heart failure and normal sinus rhythm? J Am Coll Cardiol 1997; 29:1206-13.
2. The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. Engl J Med 1997; 336:525-533.
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