Despite the introduction of a variety of new classes of drugs for the management of
heart failure,
digoxin continues to have an important role in long-term outpatient management. A wide variety of placebo-controlled clinical trials have unequivocally shown that treatment with
digoxin can improve symptoms, quality of life, and exercise tolerance in patients with mild, moderate, or severe
heart failure. These benefits are evident regardless of the underlying rhythm (normal sinus rhythm or
atrial fibrillation), etiology of the
heart failure, or concomitant
therapy (eg.
ACE inhibitors). Unlike other agents with positive inotropic properties,
digoxin does not increase all-cause mortality and has a substantial benefit in reducing
heart failure hospitalizations. Consensus guidelines have recently been published by the
Heart Failure Society of America and the American College of Cardiology/American Heart Association, and they contain the following recommendations for
digoxin treatment: 1.
Digoxin should be considered for the outpatient treatment of all patients who have persistent symptoms of
heart failure (NYHA class II-IV) despite conventional pharmacologic
therapy with
diuretics,
ACE inhibitors, and a beta-blocker when the
heart failure is caused by systolic dysfunction (the strength of evidence = A for NYHA class II and III; strength of evidence = C for NYHA class IV). 2.
Digoxin is not indicated as primary treatment for the stabilization of patients with acutely decompensated
heart failure. (Strength of evidence = B).
Digoxin may be initiated after emergent treatment of
heart failure has been completed in an effort to establish a long-term treatment strategy. 3.
Digoxin should not be administered to patients who have significant sinus or
atrioventricular block, unless the block has been treated with a permanent pacemaker (strength of evidence = B). The
drug should be used cautiously in patients who receive other agents known to depress sinus or atrioventricular nodal function (such as
amiodarone or a beta-blocker) (strength of evidence = B). 4. The dosage of
digoxin should be 0.125-0.25 mg daily in the majority of patients (strength of evidence = C). The lower dose should be used in patients over 70 years of age, those with impaired renal function, or those with a low lean body mass. Higher doses (eg,
digoxin 0.375-0.50 mg daily) are rarely needed. Loading doses of
digoxin are not necessary during initiation of
therapy for patients with chronic
heart failure. 5. Serial assessment of serum
digoxin levels is unnecessary in most patients. The radioimmunoassay was developed to assist in the evaluation of toxicity, not the efficacy of the
drug. There appears to be little relationship between serum
digoxin concentration and the
drug's
therapeutic effects. 6.
Digoxin toxicity is commonly associated with serum levels >2 ng/mL but may occur with lower
digoxin levels if
hypokalemia, hypomagnesemia, or
hypothyroidism coexist. Likewise, the concomitant use of agents such as
quinidine, verapamil,
spironolactone,
flecainide, and
amiodarone can increase serum
digoxin levels and increase the likelihood of
digoxin toxicity. 7. For patients with
heart failure and
atrial fibrillation with a rapid ventricular response, the administration of high doses of
digoxin (>0.25 mg daily) for the purpose of rate control is not recommended. When necessary, additional rate control should be achieved by the addition of beta-blocker
therapy or
amiodarone (strength of evidence = C). If
amiodarone is added, the dose of
digoxin should be reduced. Digitalis preparations are now entering their fourth century of clinical use for the treatment of chronic
heart failure symptoms. Its clinical efficacy can no longer be doubted and its safety has been verified by the multicenter DIG trial. Future advances in pharmacogenetics should facilitate identification of those patients most likely to benefit from its pharmacologic effects.