Diuretic Strategy and Renal Function in Acute Decompensated Heart Failure

A prospective, double-blind, randomized controlled study published in the March 3, 2011, issue of the New England Journal of Medicine [2011;364(9):797-805] found no differences in patients’ global assessment of symptoms or renal function with different strategies for furosemide administration in patients with acute decompensated heart failure. The DOSE (Diuretic Optimization Strategies Evaluation) study was conducted by the National Heart, Lung, and Blood Institute’s Heart Failure Clinical Research Network. Study authors noted that while loop diuretics such as furosemide are essential to the management of patients with acute decompensated heart failure, insufficient data are available to consistently guide dosing and mode of administration. Consequently, there are wide variations in loop diuretic dosing and administration in clinical practice, they explained. Patient eligibility criteria included presentation within the previous 24 hours with acute decompensated heart failure, diagnosed on the basis of at least 1 symptom (dyspnea, orthopnea, or edema) and 1 sign (rales, peripheral edema, ascites, or pulmonary congestion on chest radiography) of heart failure. In addition, eligible patients had a history of chronic heart failure and were receiving an oral loop diuretic for at least 1 month prior to hospitalization (at a dose of 80-240 mg furosemide daily, or equivalent dosing with another loop diuretic). Patients were excluded if they had a systolic blood pressure of <90 mm Hg or a serum creatinine level of >3.0 mg/dL, or if they required intravenous (IV) vasodilators or inotropic agents (other than digoxin) for heart failure management. Enrolled patients were randomized to receive 1 of 4 strategies (low- or high-dose furosemide, IV bolus or continuous infusion furosemide). The low-dose strategy was defined as a total IV furosemide dose equal to usual daily equivalent oral loop diuretic dose; the high-dose strategy was defined as a total IV furosemide dose 2.5 times their usual daily equivalent oral loop diuretic dose. Patients received furosemide either by IV bolus every 12 hours or by continuous IV infusion. The primary end points of the trial were efficacy, determined by patients’ global assessment of symptoms (measured serially from baseline to 72 hours by a visual analog scale), and safety, determined by the change in serum creatinine level from baseline to 72 hours. A total of 308 patients were enrolled in the study, with a mean age of 66 years, a 27% female population, and a 25% black population. Patients receiving IV bolus furosemide were more likely to require a dose increase at 48 hours, compared with those receiving continuous IV infusion. However, there was no difference between these diuretic strategies in the likelihood of switching to oral diuretics at 48 hours. Median total diuretic dosing over the 72-hour administration period was 592 mg in the IV bolus group and 480 mg in the continuous IV infusion group. Patients receiving high-dose furosemide were more likely to switch to oral diuretics at 48 hours than those receiving low-dose furosemide. Researchers identified no significant differences between IV bolus and continuous infusion dosing, or between high- and low-dose furosemide, in terms of the primary efficacy and safety end points. They did note that the high-dose strategy resulted in greater relief of dyspnea, greater fluid loss and weight loss, and fewer serious adverse events. The study found transient worsening of renal function with high-dose furosemide, reflecting a commonly voiced concern regarding higher dose diuretics, but no evidence of worse clinical outcomes at 60 days in the high-dose group compared with the low-dose group. The researchers suggested that previous reports of poor outcomes with high-dose diuretics may reflect the severity of the illness, as opposed to a direct effect of the higher diuretic dosing. Because of the severity of illness in the population studied, the investigators stressed that their findings may not be applicable to patients with newly diagnosed heart failure or lower diuretic requirements. Also, the trial allowed for adjustments in diuretic strategies after 48 hours of the randomly assigned strategy, which could have influenced observed differences between groups.