Target Digoxin Serum Level in Patients with Heart Failure and Atrial Fibrillation
The target serum digoxin concentration in patients with both heart failure and atrial fibrillation should be maintained between 0.5 and 0.9 ng/mL, which is lower than previously recommended ranges. 1
Rationale for Lower Target Range
The therapeutic serum concentration of digoxin has been revised downward in recent guidelines based on evidence showing:
- Higher serum concentrations (≥1.2 ng/ml) are associated with a 56% increased hazard of mortality compared to patients not on digoxin 2
- Each 0.5 ng/ml increase in serum digoxin concentration is associated with a 19% higher adjusted hazard of death 2
- Beneficial effects of cardiac glycosides in heart failure are related to neurohumoral alterations achieved at low digoxin concentrations, while high serum levels are associated with increased mortality 3
Dosing Considerations
Initial Dosing
- Standard maintenance dose: 0.125-0.25 mg daily for most patients 1
- Lower doses (0.125 mg daily or every other day) should be used for:
- Patients over 70 years of age
- Those with impaired renal function
- Patients with low lean body mass 1
Dose Adjustment Based on Renal Function
- Renal function significantly impacts digoxin clearance and should guide dosing
- The deindexed eGFR using the MDRD equation shows the highest correlation with digoxin trough concentrations 4
- Median digoxin trough concentrations by renal function:
- eGFR ≥60 ml/min: 0.60 ng/ml
- eGFR 45-59 ml/min: 0.77 ng/ml
- eGFR 30-44 ml/min: 0.97 ng/ml
- eGFR <30 ml/min: 1.30 ng/ml 4
Monitoring Recommendations
- Check serum digoxin levels 6-24 hours after administration 1
- Sampling should be done just before the next scheduled dose to allow adequate time for equilibration between serum and tissue 5
- If sampling at 24 hours is not possible, levels will be 10-25% lower than if sampled at 8 hours, depending on renal function 5
- Regular monitoring of serum electrolytes (especially potassium) and renal function is mandatory 6, 1
Clinical Goals When Using Digoxin
- Control ventricular rate at rest (<80 bpm) and during exercise (<110-120 bpm) 6, 1
- Improve ventricular function and patient well-being 6
- Reduce heart failure hospitalizations 6
Important Considerations and Precautions
Drug Interactions
- Reduce digoxin dose by 30-50% when used with amiodarone 1
- Reduce dose by at least 50% when used with dronedarone 1
- Other drugs that may increase digoxin levels: quinidine, verapamil, spironolactone, flecainide 7
Contraindications
- Second or third-degree heart block without pacemaker
- Pre-excitation syndromes (WPW syndrome)
- Previous evidence of digoxin intolerance 1
Signs of Toxicity
- Confusion, nausea, anorexia, visual disturbances (color vision changes)
- Cardiac arrhythmias 6
- Toxicity is associated with levels >2.0 ng/mL but may occur at lower levels with electrolyte abnormalities 1, 7
Ongoing Research
The DECISION trial is currently investigating the efficacy and safety of low-dose digoxin (target serum concentration 0.5-0.9 ng/ml) in patients with chronic heart failure and reduced or mildly reduced LVEF, including both patients with sinus rhythm and atrial fibrillation 8. This study may provide additional evidence regarding optimal digoxin dosing in the future.