Digoxin Calculator

Digoxin dosing tool for heart failure and atrial fibrillation

ClinCalc.com » Cardiology » Digoxin Calculator for Heart Failure and Atrial Fibrillation

About This Calculator

This calculator uses two different equations depending on the patient's comorbidities:

• Heart failure (without arrhythmias): Historically, the Jelliffe¹ and Koup and Jusko^2,3 methods have been commonly used; however, these equations target a higher digoxin concentration that may be inappropriate on the basis on the data from the Digitalis Investigation Group (DIG) post-hoc analysis.⁴ For this reason, this calculator is based on a newer equation and nomogram published by Bauman and DiDomenico,⁵ which targets a more appropriate digoxin concentration of 0.7 ng/mL and has been shown to be more accurate than other estimation methods in a modern heart failure population.^2,3
• Atrial fibrillation: Historically, the Jelliffe¹ equation has been used, but is less accurate in patients with impaired renal function. Therefore, this calculator uses the methods described by Koup and Jusko.^2,3
• Heart failure with atrial fibrillation: There is insufficient data regarding the appropriate digoxin concentration for patients with heart failure and concomitant atrial fibrillation. The DIG trial⁶ specifically excluded patients with atrial fibrillation, which limits the external validity of the DIG trial findings to this patient population. For this reason, this calculator uses the Koup and Jusko method^2,3 for these patients.

Of note, these equations utilize an ideal body weight equation⁷ to estimate lean body weight, which has been shown to be most predictive of appropriate dosing, even in morbidly obese patients.⁸

Bauman-DiDomenico Nomogram

As mentioned above, this calculator uses the Bauman-DiDomenico nomogram for dosing heart failure patients (without arrhythmias). This nomogram, shown below, is specifically intended for a more appropriate digoxin concentration of 0.7 ng/mL and has been shown to be more accurate than the traditional Jellife or Koup and Jusko methods.⁵

This calculator is not appropriate for the following patient populations:

• Significant drug interactions (eg, amiodarone, quinidine, verapamil, or macrolide antibiotics)
• End-stage renal disease on hemodialysis
• Acute renal failure or unstable renal function

The following bioavailabilities (F) are used for calculation:

• Tablet = 0.75
• Intravenous = 1
• Elixir = 0.8

Clinical Evidence for Digoxin in Heart Failure

Digitalis glycosides, like digoxin, have been used for more than 200 years to treat heart failure, but until recently, have had little clinical evidence to support their use in heart failure. In 1993, the PROVED⁹ and RADIANCE¹⁰ trials were published, which showed improvement in surrogate endpoints for heart failure. Interestingly, these trials showed that there may not be a difference in clinical efficacy between lower digoxin concentrations (eg, less than 0.9 ng/mL) and higher concentrations.¹¹

In 1997, the Digitalis Investigation Group (DIG) trial was published,⁶ which showed no improvement in mortality among patients with systolic heart failure (EF ≤ 45%) and normal sinus rhythm; however, the trial did show a decrease of 6.2% in overall hospitalizations. At the time of the trial, target digoxin concentrations were 0.5 to 2 ng/mL, which was primarily based on the drug’s toxicity rather than its efficacy.¹²

Following the publication of the DIG trial, a post-hoc analysis was published in 2003 examining the association of digoxin concentrations on the endpoints in the DIG trial.⁴ This analysis found that patients with a low digoxin concentration (0.5 to 0.8 ng/mL) showed a 6.3% reduction in mortality, patients with an intermediate concentration (0.9 to 1.1 ng/mL) showed no difference in mortality, and patients with a high concentration (> 1.2 ng/mL) showed an 11.8% increase in mortality. Although these findings are post-hoc and retrospective, it has led to a recommendation for lower goal digoxin concentrations. Additional post-hoc analyses of the DIG trial have found similar findings.¹³

Digoxin Steady-State Concentrations

The clinical evidence support the theory that digoxin exerts a beneficial effect in heart failure via neurohormonal modulation at lower serum concentrations; however, it may exert a harmful effect via inotropic stimulation at higher serum concentrations. Based on these findings, the most recent ACC/AHA full guidelines recommend a digoxin concentration of 0.5 to 1 ng/mL.¹⁴ Similarly, the HFSA 2010 guidelines suggest a concentration < 1 ng/mL (generally 0.7 to 0.9 ng/mL).¹⁵

Note that in clinical practice, serum digoxin concentrations should be drawn at least 6 hours following oral digoxin administration to allow for drug distribution.⁵ Furthermore, a steady-state concentration requires at least 1 week of consistent daily dosing in patients with normal renal function, or at least 1 month of consistent daily dosing in patients with reduced renal function (eg, creatinine clearance less than 90 mL/min).

References and Additional Reading