In patients with acute decompensated heart failure, outcomes are essentially the same regardless of whether diuretic therapy is administered in continuous infusions or boluses, and at high or low doses, according to a report in the March 3 New England Journal of Medicine.
In a prospective, double-blind, randomized trial, both patients’ own global assessments of their symptoms and objective changes in several measures of renal and cardiac function were similar, regardless of diuretic treatment approach, said Dr. G. Michael Felker of Duke University Heart Center, Durham, N.C., and his associates in the Diuretic Optimization Strategies Evaluation (DOSE) study.
The National Heart, Lung, and Blood Institute funded the DOSE trial because even though intravenous loop diuretics are "an essential component of current treatment and are administered to approximately 90% of patients hospitalized with heart failure," there is still widespread uncertainty about the best type of dosing and mode of administration. "Despite decades of clinical experience with these agents, prospective data to guide the use of loop diuretics are sparse, and current guidelines are based primarily on expert opinion. As a result, clinical practice varies widely," the investigators said.
The 308 patients were hospitalized at 26 clinical sites in the United States and Canada for acute decompensated heart failure. The mean patient age was 66 years; 27% were women, and 25% were black. Approximately three-quarters of the subjects had been hospitalized for heart failure during the preceding year. Most had moderate renal dysfunction, elevated levels of natriuretic peptide, and a decreased ejection fraction.
The subjects were randomly assigned to either a low-dose strategy in which the total daily IV furosemide dose was equivalent to their total daily oral diuretic dose, or a high-dose strategy in which the total daily IV furosemide dose was equivalent to 2.5 times their total daily diuretic dose. They also were randomly assigned to receive furosemide by either an IV bolus every 12 hours or by a continuous IV infusion.
Patients were assessed at baseline, 72 hours, and 60 days. The primary efficacy end point was the patient’s global assessment of symptoms from baseline through 72 hours, and the primary safety end point was the change in serum creatinine level from baseline to 72 hours.
There were no significant differences among the four study groups in either of these end points. There also were no significant differences across a variety of secondary end points, including dyspnea, change in body weight, net fluid loss, percentage of patients affected by congestion, worsening renal function, worsening heart failure, or changes in several biomarkers, Dr. Felker and his colleagues said (N. Engl. J. Med. 2011;364:797-805).
There was a trend toward greater improvement of patient-reported global symptoms with the high-dose strategy, but this did not reach statistical significance. Moreover, this potential benefit was offset by a higher incidence of transient worsening renal function that also did not reach statistical significance.
The median length of stay was 5 days in all four groups. A total of 130 patients (42%) died, required rehospitalization, or required a visit to the emergency department within 60 days, but there were no significant differences among the treatment groups in this composite end point. The total number of patients who were alive and not hospitalized at 60 days also did not differ significantly among the four groups.
The DOSE study was funded by the National Heart, Lung, and Blood Institute. Dr. Felker and his associates reported numerous ties to drug and device companies, including those that manufacture diuretics.