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Review of randomized trials of digoxin therapy in patients with chronic heart failure
1Henry Ford Heart and Vascular Institute, Henry Ford Hospital, Detroit, Michigan 48202.
Insights
Digoxin improves heart function and exercise capacity in congestive heart failure (CHF) patients. While not improving survival, it remains a valuable oral inotropic agent, especially with ACE inhibitors.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Digoxin has been used for over 200 years to treat cardiac conditions.
- Its precise role in multidrug therapy for congestive heart failure (CHF) remains debated.
- Recent trials have focused on digoxin's efficacy in moderate CHF with sinus rhythm.
Purpose of the Study:
- To evaluate the benefits of digoxin in patients with moderate CHF and sinus rhythm.
- To compare digoxin's effects with ACE inhibitors.
- To assess the value of combining digoxin with ACE inhibitors.
Main Methods:
- Double-blind, randomized, placebo-controlled trials.
- Evaluation of left ventricular ejection fraction and exercise capacity.
- Assessment of CHF worsening and clinical compensation.
Main Results:
- Digoxin improved left ventricular ejection fraction and exercise capacity compared to placebo.
- Digoxin demonstrated benefits similar to ACE inhibitors in clinical compensation and LV function.
- Improved survival was only demonstrated with ACE inhibitors.
Conclusions:
- Digoxin is superior to placebo in improving cardiac function and exercise tolerance in CHF.
- Digoxin is currently the only oral inotropic agent considered useful in CHF treatment.
- Digoxin, alone or with ACE inhibitors, appears beneficial for CHF patients with systolic LV dysfunction.
Abstract:
Although digitalis glycosides were introduced in the treatment of cardiac maladies greater than 200 years ago, controversy persists regarding the precise role of digoxin in any multidrug approach to the treatment of congestive heart failure (CHF). Despite its widespread use for more than 2 centuries, only recently have double-blind, randomized, placebo-controlled trials of digoxin therapy been conducted in patients with moderate CHF and sinus rhythm. These trials demonstrate that digoxin is superior to placebo in improving left ventricular (LV) ejection fraction, increasing exercise capacity, and preventing CHF worsening. Digoxin produces benefits similar to those seen with angiotensin converting enzyme (ACE) inhibitors with regard to clinical compensation and improvement in LV function. However, improved survival is demonstrated only in response to ACE inhibitors. The recently completed RADIANCE study addresses the value of combining digoxin with ACE inhibitor therapy in patients with mild-to-moderate CHF. Because increased mortality has been reported with the newer oral inotropic agents, it currently appears that digoxin is the only oral inotropic agent useful in clinical practice in the treatment of CHF. However, the effects of digoxin on mortality in patients with CHF remain unknown. In the large, double-blind, randomized trial conducted by the National Heart, Lung, and Blood Institute, the effects of digoxin on mortality in patients with CHF and already being treated with ACE inhibitors are currently being evaluated. Presently, based on the results of placebo-controlled studies, it appears that digoxin, alone or in combination with ACE inhibitors, is beneficial in patients with any signs or symptoms of CHF due to systolic LV dysfunction.