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Diuretic Strategies in Patients With Acute Decompensated Heart Failure
Study Questions:
How does intravenous furosemide given as a bolus every 12 hours compare with 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) in acute decompensated heart failure (ADHF)?
Methods:
This was a prospective, double-blind, randomized trial, where 308 patients with ADHF received 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). Specified dose adjustments were allowed after 48 hours. The 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 were coprimary endpoints of the study.
Results:
When bolus administration was compared 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/dl [4.4 ± 26.5 μmol/L] and 0.07 ± 0.3 mg/dl [6.2 ± 26.5 μmol/L], respectively; p = 0.45). When the investigators compared 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/dl [7.1 ± 26.5 μmol/L] with the high-dose strategy and 0.04 ± 0.3 mg/dl [3.5 ± 26.5 μmol/L] 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:
The study authors concluded that there were no significant differences in symptoms or in the change in renal function when intravenous furosemide therapy was administered by bolus as compared with continuous infusion, or at a high dose as compared with a low dose in patients with ADHF.
Perspective:
This study is important because it suggests that the diuretic regimen or dose has little impact on symptoms or renal function in ADHF. Evaluating the impact of any therapy in ADHF is challenging because heart failure is often accompanied by altered renal function (J Am Coll Cardiol 2008;52:1527-39; Heart Fail Clin 2010;6:xi-xvi). Recognizing these challenges, a recent consensus conference classified cardiorenal syndromes into five subtypes with distinct pathophysiologies, prevention, and management strategies (Eur Heart J 2010;31:703-11). Further studies are required to determine whether identifying the subtype of cardiorenal syndrome in ADHF has better predictive value in determining the response to the type of diuretic regimen.
Keywords: Heart Diseases, National Heart, Lung, and Blood Institute (U.S.), Cardio-Renal Syndrome, Diuretics, Heart Failure, United States
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