Diuretic strategies in patients with acute decompensated heart failure

Abstract

Background: Loop diuretics are an essential component of therapy for patients with acute decompensated heart failure, but there are few prospective data to guide their use.

Methods: In a prospective, double-blind, randomized trial, we assigned 308 patients with acute decompensated heart failure to receive furosemide administered intravenously by means of either a bolus every 12 hours or continuous infusion and at either a low dose (equivalent to the patient's previous oral dose) or a high dose (2.5 times the previous oral dose). The protocol allowed specified dose adjustments after 48 hours. The coprimary end points were patients' global assessment of symptoms, quantified as the area under the curve (AUC) of the score on a visual-analogue scale over the course of 72 hours, and the change in the serum creatinine level from baseline to 72 hours.

Results: In the comparison of bolus with continuous infusion, there was no significant difference in patients' global assessment of symptoms (mean AUC, 4236±1440 and 4373±1404, respectively; P=0.47) or in the mean change in the creatinine level (0.05±0.3 mg per deciliter [4.4±26.5 μmol per liter] and 0.07±0.3 mg per deciliter [6.2±26.5 μmol per liter], respectively; P=0.45). In the comparison of the high-dose strategy with the low-dose strategy, there was a nonsignificant trend toward greater improvement in patients' global assessment of symptoms in the high-dose group (mean AUC, 4430±1401 vs. 4171±1436; P=0.06). There was no significant difference between these groups in the mean change in the creatinine level (0.08±0.3 mg per deciliter [7.1±26.5 μmol per liter] with the high-dose strategy and 0.04±0.3 mg per deciliter [3.5±26.5 μmol per liter] with the low-dose strategy, P=0.21). The high-dose strategy was associated with greater diuresis and more favorable outcomes in some secondary measures but also with transient worsening of renal function.

Conclusions: Among patients with acute decompensated heart failure, there were no significant differences in patients' global assessment of symptoms or in the change in renal function when diuretic therapy was administered by bolus as compared with continuous infusion or at a high dose as compared with a low dose. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00577135.).

Figure 1. Patients' Global Assessment of Symptoms during the 72-Hour Study-Treatment Period

Patients' global assessment of symptoms was measured with the use of a visual-analogue scale and quantified as the area under the curve (AUC) of serial assessments from baseline to 72 hours. Mean (±SD) AUCs are shown for the group that received boluses every 12 hours as compared with the group that received a continuous infusion (Panel A) and for the group that received a low dose of the diuretic (equivalent to the patients' previous oral dose) as compared with the group that received a high dose (2.5 times the previous oral dose) (Panel B). Plus–minus values are means ±SD.

Figure 2. Mean Change in Serum Creatinine Level

The mean change in the serum creatinine level over the course of the 72-hour study-treatment period is shown for the group that received boluses every 12 hours as compared with the group that received a continuous infusion and for the group that received a low dose of the diuretic (equivalent to the patients' previous oral dose) as compared with the group that received a high dose (2.5 times the previous oral dose). To convert the values for creatinine to micromoles per liter, multiply by 88.4.

Figure 3. Kaplan–Meier Curves for the Clinical Composite End Point of Death, Rehospitalization, or Emergency Department Visit

Kaplan–Meier curves are shown for death, rehospitalization, or emergency department visit during the 60-day follow-up period in the group that received boluses every 12 hours as compared with the group that received a continuous infusion (Panel A) and in the group that received a low dose of the diuretic (equivalent to the patients' previous oral dose) as compared with the group that received a high dose (2.5 times the previous oral dose) (Panel B).