Recommendation 37: We suggest digoxin be considered in patients with HFrEF in sinus rhythm who continue to have moderate to severe symptoms, despite appropriate doses of guideline-directed medical therapy (GDMT) to relieve symptoms and reduce hospitalizations (Weak Recommendation, Moderate Quality Evidence).

Values and preferences: These recommendations place a high value on the understanding that the use of cardiac glycosides in HFrEF remains controversial in light of contemporary therapy, and digoxin had no effect on mortality, CV hospitalizations, exercise or the primary endpoint in the DIG trial. Digoxin can cause atrial and ventricular arrhythmias particularly in the presence of hypokalemia or in the presence of worsening of renal function (with increased digoxin levels).

• In patients receiving digoxin, serum potassium and creatinine should be measured with increases in digoxin or diuretic dose, addition or discontinuation of an interacting drug, or during a dehydrating illness, to reduce the risk of digoxin toxicity. Patients with reduced or fluctuating renal function, the elderly, those with low body weight, and women are at increased risk of digoxin toxicity and might require more frequent monitoring including digoxin levels.
• Routine digoxin levels are not required other than to assess for digoxin toxicity. Digoxin levels should not be used to guide chronic therapy. Titration to digoxin levels has not been tested in clinical trials.