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±26.5μmol 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.)

Outcomes Associated With a Strategy of Adjuvant Metolazone or High‐Dose Loop Diuretics in Acute Decompensated Heart Failure: A Propensity Analysis

“…Although there is a lack of randomized data to specifically answer this question, the DOSE (Diuretic Optimization Strategies Evaluation) trial provides support for the safety and efficacy of intravenous HDLDs. In this 308 ADHF patient population, patients randomized to intravenous HDLD received an average of 773 mg of intravenous furosemide in 72 hours and experienced greater fluid and weight loss, a greater incidence of WRF, but without any worsening in death or rehospitalization 23. In our study using propensity score adjustment to reduce confounding by indication, we found similar findings with a greater incidence of WRF but no survival disadvantage.…”

“…However, when the use of HDLDs were subjected to the same analytic methodology, there was no risk for hyponatremia, hypokalemia, or mortality. In light of the existing randomized trial data to support the safety of aggressive loop diuretic dosing,23 and the currently presented findings suggesting a mortality disadvantage with metolazone as well as an increased risk of electrolyte disturbances and WRF, routine escalation of loop diuretic doses may be the preferred approach for the management of ADHF until adequately powered trials are available to more definitively inform this question.…”

Pro‐Inflammatory Biomarkers in Stable Versus Acutely Decompensated Heart Failure With Preserved Ejection Fraction

“…We measured IL‐6, TNF‐α, and hs‐CRP and PTX3 in age and sex‐matched cohorts of HFpEF patients from 3 prospective, placebo‐controlled, randomized clinical trials conducted by the NHLBI Heart Failure Research Network, RELAX (Effect of Phosphodiesterase‐5 Inhibition on Exercise Capacity and Clinical Status in Heart Failure with Preserved Ejection Fraction),37 DOSE (Diuretic Strategies in Patients With Acute Decompensated Heart Failure)38 and ROSE (Renal Optimization Strategies Evaluation) 39. RELAX included S‐HFpEF patients while DOSE and ROSE included acutely decompensated HF (ADHF) patients with both HFrEF and HFpEF.…”

Worsening renal function definition is insufficient for evaluating acute renal failure in acute heart failure

“…It is clear that patients with pre‐existing renal dysfunction are vulnerable to developing renal dysfunction on diuretic administration 21, 22. Furthermore, bolus infusions do not promote gradual diuresis and therefore do not allow time for the fluid in the periphery to move from the extravascular to the intravascular space, which leads to intravascular volume depletion and significant drops in renal perfusion, subsequently leading to renal dysfunction 23. Aggressive decongestion therefore leads to transit renal dysfunction during the acute phase of AHF; however, current research suggested that transient renal dysfunction with the use of high‐dose diuretics was associated with early clinical improvement and not a poor outcome 23, 24.…”