DIGOXIN THERAPY IN CHRONIC HEART-FAILURE

Digitalis has been used for more than 250 years, but its role in the t reatment of chronic heart failure has been intensively investigated on ly during the past two decades. Digoxin increases cardiac output both at rest and during exercise, alone or in combination with ACE inhibito rs, and these hemodynamic effects are sustained during chronic therapy . A daily dose of digoxin that achieves a serum concentration of appro ximately 1.2 ng/ml is associated with a significant improvement in cen tral hemodynamics, particularly in patients with impaired cardiac func tion despite pretreatment with diuretics and ACE inhibitors. Acute adm inistration of digoxin in patients with chronic heart failure has an i mmediate sympathoinhibitory effect, and chronic therapy is associated with a sustained decrease in serum norepinephrine concentration. Disco ntinuation of digoxin in patients with chronic heart failure resulted in hemodynamic deterioration, which was reversed when the drug was rea dministered. Randomized withdrawal of digoxin in patients receiving on ly diuretics (PROVED study), or its withdrawal in patients receiving d iuretics and ACE inhibitors (RADIANCE study), was associated with wors ening of the clinical evidence of heart failure and a decrease in left ventricular systolic function in both studies. In the only large-scal e, placebo-controlled mortality study reported thus for (DIG Trial), 7 788 patients received standard drug treatment for chronic heart failur e in addition to either digoxin or placebo. Digoxin had no impact on s urvival over the 37 months of follow-up, but the incidence of hospital izations due to worsening heart failure was significantly reduced in p atients receiving the drug compared with those receiving placebo.