A novel dosing recommendation for digoxin in heart failure patients and a nomogram for determining the initial dose of the drug has been proposed by US scientists in order to take advantage of the drug's altered therapeutic window.
The therapeutic range for digoxin in heart failure has recently narrowed and lowered, shifting from the older window of 0.8–2.0 ng/ml to 0.5–0.9 ng/ml, or less than 1.0 ng/ml, which has been associated with lower rates of all-cause mortality and hospitalization.
Noting that dosing methods for digoxin have not changed accordingly, Jerry Bauman, from the University of Illinois at Chicago, USA, and colleagues examined and reviewed the medical records of 54 patients who achieved a steady state digoxin concentration, 85% of whom had a clinical diagnosis of heart failure.
The average age of the patients was 68 years, and 56% were men. The average creatinine clearance was 50 ml/min and the average ideal body weight was 62 kg. In addition, the average daily dose of digoxin was 0.132 mg, while the average steady state digoxin concentration was 0.9 ng/ml.
Using these variables, the researchers generated an equation that related them to a specific target digoxin concentration of 0.7 ng/ml, using the results to construct a dosing nomogram. This novel method was then compared with two existing models: the Jelliffe method and the Koup and Jusko method.
Analysis revealed that the novel method and the Koup and Jusko method could more accurately predict digoxin concentrations than the Jelliffe method. Specifically, the root mean square error for the Jelliffe method, using ideal body weight, was 0.810, compared with 0.401 for the Koup and Jusko method, using heart failure, and 0.375 for the novel method.
The team concludes: "Given the importance of maintaining the digoxin concentration within the narrow window associated with improved mortality, we propose using our dosing guidelines to determine the initial dose of digoxin.
"Subsequently, the digoxin concentration should be monitored and the dose of digoxin adjusted to ensure that the steady state dose results in trough concentrations of 0.5–0.9 ng/ml."
The research is published in the Archives of Internal Medicine.
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