Effect of Admission Oral Diuretic on IV Diuretic in Acute HF
Background Results from the DOSE-AHF study suggest that an initial continuous infusion of loop diuretics is not superior to bolus dosing with regard to clinical endpoints in acute heart failure. We hypothesized that outpatient furosemide dose was associated with congestion and poorer renal function and explored the hypothesis that a continuous infusion may be more effective in patients on higher outpatient diuretic doses.
Methods The DOSE-AHF study randomized 308 patients within 24 hours of admission to high versus low initial intravenous diuretic dose given as either a continuous infusion or bolus. We compared baseline characteristics and assessed associations between mode of administration (bolus vs continuous) and outcomes in patients receiving high-dose (≥120 mg furosemide equivalent, n = 177) versus low-dose (<120 mg furosemide equivalent, n = 131) outpatient diuretics.
Results Patients on higher doses of furosemide were less frequently on renin-angiotensin system inhibitors (P = .01) and had worse renal function and more advanced symptoms. There was a significant interaction between outpatient dose and mode of therapy (P = .01) with respect to net fluid loss at 72 hours after adjusting for creatinine and intensification strategy. Admission diuretic dose was associated with an increased risk of death or rehospitalization at 60 days (adjusted hazard ratio 1.08 per 20-mg increment in dose, 95% CI 1.01–1.16, P = .03).
Conclusions In acute heart failure, patients on higher diuretic doses have greater disease severity and may benefit from an initial bolus strategy.
Despite lack of evidence of clinical benefit (and potential harm) in chronic heart failure (HF), loop diuretics remain a cornerstone of decongestive therapy in acute HF (AHF). Diuretic escalation is used in the outpatient setting to prevent HF admission but can be associated with worsening renal function, neurohormonal activation, diuretic refractoriness, and worse outcomes. The proposed explanation for diuretic dose escalation is multifactorial, including progressive renal dysfunction, bowel wall edema from elevation of systemic venous pressures, and increased renal absorption of sodium during intradosing periods. Before the publication of the results of the DOSE-AHF trial, data primarily from small observational studies and meta-analyses suggested that continuous infusion diuretic therapy was more effective than intravenous boluses at decongestion, without compromising renal function.
The DOSE-AHF study was the first randomized clinical trial to address the hypothesis that mode of diuretic therapy may affect decongestion, renal function, and clinical outcomes in acute decompensated HF. Using a 2-by-2 factorial design, 308 patients were randomly assigned within 24 hours of HF admission to receive high-dose versus low-dose and continuous versus bolus intravenous diuretics at either dose. There were no differences in symptom relief, renal function, net fluid loss, or death and rehospitalization at 60 days between patients receiving bolus versus continuous infusion diuretics. Despite the overall neutral results with regard to diuretic strategy (bolus vs continuous), we sought to test the hypothesis that outpatient furosemide dose may be associated with markers of congestion and worsening renal function in patients with AHF. Furthermore, we hypothesized that patients with acute decompensated HF may respond differentially to bolus versus continuous infusion diuretic therapy as a function of outpatient diuretic dose.
Abstract and Introduction
Abstract
Background Results from the DOSE-AHF study suggest that an initial continuous infusion of loop diuretics is not superior to bolus dosing with regard to clinical endpoints in acute heart failure. We hypothesized that outpatient furosemide dose was associated with congestion and poorer renal function and explored the hypothesis that a continuous infusion may be more effective in patients on higher outpatient diuretic doses.
Methods The DOSE-AHF study randomized 308 patients within 24 hours of admission to high versus low initial intravenous diuretic dose given as either a continuous infusion or bolus. We compared baseline characteristics and assessed associations between mode of administration (bolus vs continuous) and outcomes in patients receiving high-dose (≥120 mg furosemide equivalent, n = 177) versus low-dose (<120 mg furosemide equivalent, n = 131) outpatient diuretics.
Results Patients on higher doses of furosemide were less frequently on renin-angiotensin system inhibitors (P = .01) and had worse renal function and more advanced symptoms. There was a significant interaction between outpatient dose and mode of therapy (P = .01) with respect to net fluid loss at 72 hours after adjusting for creatinine and intensification strategy. Admission diuretic dose was associated with an increased risk of death or rehospitalization at 60 days (adjusted hazard ratio 1.08 per 20-mg increment in dose, 95% CI 1.01–1.16, P = .03).
Conclusions In acute heart failure, patients on higher diuretic doses have greater disease severity and may benefit from an initial bolus strategy.
Introduction
Despite lack of evidence of clinical benefit (and potential harm) in chronic heart failure (HF), loop diuretics remain a cornerstone of decongestive therapy in acute HF (AHF). Diuretic escalation is used in the outpatient setting to prevent HF admission but can be associated with worsening renal function, neurohormonal activation, diuretic refractoriness, and worse outcomes. The proposed explanation for diuretic dose escalation is multifactorial, including progressive renal dysfunction, bowel wall edema from elevation of systemic venous pressures, and increased renal absorption of sodium during intradosing periods. Before the publication of the results of the DOSE-AHF trial, data primarily from small observational studies and meta-analyses suggested that continuous infusion diuretic therapy was more effective than intravenous boluses at decongestion, without compromising renal function.
The DOSE-AHF study was the first randomized clinical trial to address the hypothesis that mode of diuretic therapy may affect decongestion, renal function, and clinical outcomes in acute decompensated HF. Using a 2-by-2 factorial design, 308 patients were randomly assigned within 24 hours of HF admission to receive high-dose versus low-dose and continuous versus bolus intravenous diuretics at either dose. There were no differences in symptom relief, renal function, net fluid loss, or death and rehospitalization at 60 days between patients receiving bolus versus continuous infusion diuretics. Despite the overall neutral results with regard to diuretic strategy (bolus vs continuous), we sought to test the hypothesis that outpatient furosemide dose may be associated with markers of congestion and worsening renal function in patients with AHF. Furthermore, we hypothesized that patients with acute decompensated HF may respond differentially to bolus versus continuous infusion diuretic therapy as a function of outpatient diuretic dose.
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