What are the guidelines for using digoxin (digitalis glycoside) in treating heart failure and arrhythmias, such as atrial fibrillation?

Guidelines for Using Digoxin in Heart Failure and Atrial Fibrillation

Digoxin is recommended for heart rate control in atrial fibrillation with rapid ventricular response, especially in patients with heart failure and reduced ejection fraction (LVEF <40%), and can be used as an adjunctive therapy in symptomatic heart failure patients with reduced ejection fraction to reduce hospitalizations, though it has no effect on mortality. 1

Indications for Digoxin Use

Atrial Fibrillation

• First-line for initial control of ventricular rate in patients with rapid atrial fibrillation (resting heart rate >80 bpm, exercise >110-120 bpm) and heart failure with reduced ejection fraction (LVEF <40%) 1
• Should be used to control heart rate in addition to, or prior to, a beta-blocker in patients with AF and LVEF <40% (Class I recommendation, Level of Evidence C) 1
• In patients with LVEF >40% and AF, verapamil or diltiazem may be used alone or in combination with digoxin for rate control 1
• In the longer term, a beta-blocker, either alone or in combination with digoxin, is preferred for rate control in patients with LVEF <40% 1

Heart Failure with Sinus Rhythm

• For patients with symptomatic heart failure and LVEF <40% in sinus rhythm (Class IIa recommendation, Level of Evidence B) 1
• Improves ventricular function and patient well-being, reduces hospital admission for worsening heart failure by 28%, but has no effect on survival 1
• Should be used after optimal doses of ACE inhibitor/ARB, beta-blocker, and aldosterone antagonist (if indicated) 1
• FDA approved for treatment of mild to moderate heart failure 2

Dosing Guidelines

Initial Dosing

• Loading doses generally not required in stable patients 1
• Standard maintenance dose: 0.25 mg daily for adults with normal renal function 1
• Reduced dose (0.125 mg or 0.0625 mg daily) for:
  • Elderly patients 1
  • Patients with renal impairment 1, 2
  • Patients with low lean body mass 2, 3

Monitoring

• Check digoxin concentration early during chronic therapy in patients with normal renal function 1
• Therapeutic serum concentration should be between 0.6 and 1.2 ng/mL (lower than previously recommended) 1
• Serial monitoring of serum electrolytes and renal function is mandatory 1
• Regular digoxin concentration measurements have not been shown to confer better outcomes 1

Contraindications

• Second or third-degree heart block (without a permanent pacemaker) 1
• Pre-excitation syndromes 1
• Previous evidence of digoxin intolerance 1
• Caution in suspected sick sinus syndrome 1

Potential Adverse Effects

• Sinoatrial and AV block 1
• Atrial and ventricular arrhythmias, especially with hypokalemia 1
• Signs of toxicity: confusion, nausea, anorexia, and disturbance of color vision 1
• For ventricular arrhythmias caused by toxicity, digoxin-specific Fab antibody fragments should be considered 1

Drug Interactions

• Certain drugs may increase plasma digoxin levels: 2
  • Amiodarone, diltiazem, verapamil
  • Certain antibiotics
  • Quinidine
• Potassium-depleting diuretics increase risk of digitalis toxicity 2
• Calcium, particularly when administered rapidly IV, may produce serious arrhythmias in digitalized patients 2
• Concomitant use with sympathomimetics increases risk of cardiac arrhythmias 2

Special Considerations

Elderly Patients

• Elderly have reduced elimination of digoxin requiring lower doses (0.125 mg or 0.0625 mg daily) 2, 4
• Therapeutic monitoring is especially important in elderly patients 4

Electrolyte Disorders

• Maintain normal serum potassium and magnesium concentrations 2
• Hypokalemia or hypomagnesemia may cause toxicity despite serum digoxin concentrations below 2.0 ng/mL 2
• Hypercalcemia predisposes patients to digitalis toxicity 2

Renal Impairment

• Patients with impaired renal function require smaller maintenance doses 2
• Longer period required to achieve steady-state serum concentration 2
• Higher risk for toxicity with longer duration of toxic effects 2

Evidence Summary

• In the DIG trial (6,800 patients), digoxin did not alter all-cause mortality but reduced hospital admission for worsening HF by 28% 1
• Quality of life was not improved in the DIG trial 1
• No advantage shown in patients with heart failure with preserved ejection fraction (HFPEF) 1
• Recent observational studies suggest increased mortality in patients with atrial fibrillation without heart failure taking digoxin 5
• Data remains controversial for patients with both atrial fibrillation and systolic heart failure 5

By following these guidelines and carefully monitoring patients, digoxin remains a useful medication in the management of heart failure and atrial fibrillation, particularly in specific patient populations.