Differences in pharmacological property between combined therapy of the vasopressin V2-receptor antagonist tolvaptan plus furosemide and monotherapy of furosemide in patients with hospitalized heart failure

Abstract

Background: Tolvaptan has been shown to improve congestion in heart failure patients. The purpose of this study was to evaluate the pharmacology and clinical efficacy of combined tolvaptan and furosemide therapy.

Methods: This study included 40 patients with systemic volume overload who were hospitalized for heart failure. Patients who showed no improvement in the condition after receiving 20 mg intravenous furosemide were included and were randomly selected to receive tolvaptan as an add-on to furosemide or to receive an increased dose of furosemide. We evaluated the bioelectrical impedance analyzer parameters, the parameters of the inferior vena cava using echocardiography, vital signs, body weight, urine output, and laboratory data for 5 days.

Results: In the changes from baseline between intracellular water volume (ICW) and extracellular water volume (ECW) after additional use of tolvaptan or furosemide from Day 1 to Day 5, there were no significant differences observed between ICW and ECW over 5 days in the tolvaptan + furosemide group, although differences were found in the furosemide group from Day 2 onward. Changes in the respiratory collapse of inferior vena cava increased significantly, and systolic blood pressure decreased significantly only in the furosemide group.

Conclusions: The present study clearly demonstrates that combined therapy with tolvaptan and furosemide removed excess ICW and ECW to an equal extent, while furosemide alone primarily removed ECW, including intravascular water.

Keywords: Fluid compartments; Furosemide; Heart failure; Tolvaptan.