HEART FAILURE
Clinical Overview

Pharmacotherapy

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Indications Should be used routinely for severe heart failure due to left-ventricular systolic dysfunction 1 Add for mild to moderate heart failure patients who remain symptomatic after optimal ACE inhibitor and diuretic therapy 1 Improves symptoms and exercise tolerance; prevents clinical deterioration 1	Digitalis purpurea
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In the presence of normal renal function, 0.25mg daily of digoxin may be initiated and loading doses are generally not needed.¹ Patients who are elderly and/or have renal function impairment should be started at 0.125mg daily or lower and titrated to adequate dose. Steady state will be reached within 1 week with normal renal function and 2-3 weeks with renal dysfunction.

Monitoring Serial blood level monitoring unnecessary Treat the patient and not the level Draw serum digoxin level at least 6 hours after dose

Signs and symptoms of digoxin toxicity confusion nausea / vomiting / diarrhea anorexia visual disturbances headache cardiac abnormalities

Once steady state is achieved, serial blood monitoring for digoxin is not necessary unless a change in patient condition occurs such as heart failure status worsens, renal function deteriorates, additional drugs are added that could affect digoxin level, and signs and symptoms of toxicity develop (e.g., confusion, nausea, anorexia, visual disturbances).¹ It is probably reasonable to check levels yearly after steady state is achieved, but it is important to keep in mind: treat the patient and not the level. Symptoms may be controlled at "subtherapeutic" levels and increasing the dose could cause toxicity to develop in the elderly.

A study conducted by Williamson and colleagues²² examined the frequency of elevated serum digoxin levels (>2.0 ng/mL) in relation to the time postdose that the level was drawn. The study revealed that 15.9% of the elevated levels were drawn < 6 hours following the last digoxin dose. This demonstrates that some "toxic" levels are not truly elevated because they may have been drawn at an inappropriate time.

Drug Interactions quinidine verapamil amiodarone erythromycin anticholinergic agents

 
The medications listed here are a few of the agents that may increase the serum levels of digoxin. If any of these agents are started while a patient is on digoxin, a serum digoxin level should be checked about one week after the new drug is started.¹

In a large, prospective, randomized, placebo controlled, National Institute of Health (NIH)-sponsored trial, the long-term effect of digoxin on mortality from any cause and on hospitalization for heart failure was studied.²⁵ Results of this Digitalis Investigation Group (DIG) study study indicate a modest but significant reduction in hospitalization for any cause and a 10% reduction in hospitalizations due to cardiovascular causes. The primary endpoint measured was death from any cause and the investigators found that mortality rates were nearly identical in the digoxin and placebo groups. The investigators concluded that digoxin therapy in heart failure patients is likely to affect the frequency of hospitalization but not survival.

"Triple" Drug Therapy
Young and colleauges²⁶ further evaluated the PROVED and RADIANCE trials to determine if "triple" drug therapy, consisting of digoxin, ACE inhibitor, and diuretic, was superior in clinical endpoints of heart failure than diuretic alone, diuretic + ACE inhibitor, or diuretic + digoxin. In the areas of frequency of treatment failure and likelihood of deterioration in heart failure status, triple drug therapy was significantly superior to the other three drug therapy combinations. Exercise capacity and maintenance of LVEF was significantly greater in the groups treated with digoxin as opposed to those not receiving digoxin. The authors conclude that patients with symptomatic heart failure due to severe systolic dysfunction can significantly benefit with triple drug therapy in the initial management of their disease.

Neurohormonal effects of digoxin
The recent digoxin trials in heart failure have elucidated another mechanism of action for the effectiveness of this drug. Traditionally, the goal of therapy in the treatment of heart failure has been to improve the hemodynamics of the heart. Digoxin has always been known as a positive inotropic agent and effective in hemodynamic modulation in heart failure patients. However, these newer trials have used lower doses of digoxin, resulting in serum digoxin levels < 1.0 ng/mL. These lower doses have shown to be effective in the treatment of patients with milder forms of heart failure. At these low doses, digoxin does not have any inotropic effects, but has been found to have active neurohormonal effects. Thus, the initiation of digoxin therapy may not have to be reserved for the more severe heart failure patients, but may have benefits in treatment of milder forms of heart failure.²⁷

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