Heart Failure in Outpatients: A Randomized Trial of Digoxin versus Placebo

The view that digitalis clinically benefits patients with heart failure and sinus rhythm lacks support from a well-controlled study. Using a randomized, double-blind, crossover protocol, we compared the effects of oral digoxin and placebo on the clinical courses of 25 outpatients without atrial fibrillation. According to a clinicoradiographic scoring system, the seventy of heart failure was reduced by digoxin in 14 patients; in nine of these 14, improvement was confirmed by repeated trials (five patients) or right-heart catheterization (four patients). The other 11 patients had no detectable improvement from digoxin. Patients who responded to digoxin had more chronic and more severe heart failure, greater left ventricular dilation and ejection-fraction depression, and a third heart sound. Multivariate analysis showed that the third heart sound was the strongest correlate of the response to digoxin (P<0.0001). These data suggest that long-term digoxin therapy is clinically beneficial in patients with heart failure unaccompanied by atrial fibrillation whose failure persists despite diuretic treatment and who have a third heart sound. (N Engl J Med. 1982; 306:699–705.) WHETHER digitalis is beneficial to patients whose heart failure is unaccompanied by atrial fibrillation was a subject of debate during the 19th century. From 1919 to 1960, a series of clinical and hemodynamic observations suggested that this drug was useful in such patients,^{1 2 3 4 5 6 7 8 9 10 11 12} but a controlled study was never undertaken, and most observations were made in patients with untreated hypertension or valvular heart disease, neither of which is now prevalent among outpatients undergoing long-term follow-up for chronic heart failure. In the past decade many clinicians and investigators have grown skeptical that digitalis confers benefit in patients in sinus rhythm, because.