Study population:

The Digitalis Investigator Group (DIG) main study enrolled 6800 patients with heart failure and a left ventricular ejection fraction less than or equal to 45%³ and an ancillary study enrolled 988 patients with heart failure and left ventricular ejection fraction >45% from 1991 to 1993¹¹. Full inclusion and exclusion criteria have previously been described.¹² Briefly, in both studies participants had to be in normal sinus rhythm without significant renal insufficiency (creatinine > 3.0mg/dl), severe liver disease, hypokalemia (potassium <3.2mmol/l), hyperkalemia (potassium >5.5 mmol/l) or clinically relevant bradyarrhythmias without a pacemaker. Most participants (95%) were receiving angiotensin-converting-enzyme inhibitors but patients were not on routine beta-blocker or aldosterone antagonist therapy. In the main trial, digoxin was associated with reduction in heart failure hospitalizations (HR 0.72, 95% CI 0.66–0.79) with no effect on mortality (HR 0.99, 95% CI 0.91–1.07)³. In the ancillary trial, there was a non-significant trend towards reduced heart failure hospitalizations, similar in magnitude to that seen in the main study (HR 0.79, 95% CI 0.59–1.04), and no effect on mortality (HR 0.99, 95% CI 0.76–1.28)^3,11. All patients gave informed consent for the DIG studies and the Tufts Medical Center Institutional Review Board approved this post-hoc analysis.