Review of randomized trials of digoxin therapy in patients with chronic heart failure

Although digitalis glycosides were introduced in the treatment of cardiac maladies > 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 mildto-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 placebocontrolled 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.