Intermittent 6-month low-dose dobutamine infusion in severe heart failure: DICE Multicenter Trial

Background Patients with end-stage heart failure are often refractory to maximal oral therapy, and they hove high mortality rates, poor quality of life, and frequent hospitalizations with elevated health care costs. Intermittent dobutamine therapy has been suggested as an additional option in this clinical setting. Methods and Results Thirty-eight patients clinically stable for at least 48 hours with standard treatment, New York Heart Association (NYHA) functional class III or IV, cardiac index less than or equal to 2.2 L/min/m(2), and left ventricular ejection fraction less than or equal to 30% were randomly assigned to ambulatory intermittent dobutamine or optimal standard treatment. Dobutamine was infused at 2.5 mu g/kg/min with a portable pump 48 hours/week for 6 months. The primary study end point was the reduction of hospitalizations for worsening of congestive heart failure (CHF); changes in NYHA functional class, 6-minute walking test, and mortality rates were secondary end points. During the 6-month follow-up, all patients in dobutamine and control groups underwent weekly clinical visits with serum sodium and potassium measurement. Baseline characteristics were age 65 +/- 2 years, NYHA class III/IV 17/21, ejection fraction 22% +/- 1%, and cardiac index 1.89 +/- 0.1 L/min/m(2), without differences between treatment groups, Hospitalizations for all causes over a 6-month period were 17 and 11 in control and dobutamine groups; 11 of 17 and 7 of 11 were for worsening CHF. Four control patients but none in the dobutamine group had 2 or more hospitalizations for worsening of CHF. There were no significant differences in NYHA functional class and in 6-minute walking test. Three patients in the control group died and 5 in the dobutamine group died. Two patients in the dobutamine group underwent heart transplantation. Protocol was discontinued in the dobutamine group for severe ventricular arrhythmias (1 patient), infusion system failure (1 patient), and consent withdrawal (1 patient). In 3 patients in the dobutamine group, drug dose was increased to 5 mu g/kg/min because of CHF. Conclusions Six-month intermittent low-dose dobutamine administration was weil tolerated by patients with severe CHF; it did not improve the functional status and did not significantly increase the mortality rate as found with higher dobutamine doses in other studies. Hospitalizations for all causes and for worsening of CHF tended to be fewer in the dobutamine group.