Randomized pilot trial comparing tolvaptan with furosemide on renal and neurohumoral effects in acute heart failure

Abstract

AimsLoop diuretics are first‐line medications for congestive heart failure (CHF); however, they are associated with serious adverse effects, including decreased renal function, and sympathetic nervous and renin–angiotensin system activation. We tested whether tolvaptan, a vasopressin V2‐receptor antagonist, could reduce unfavourable furosemide‐induced effects during CHF treatment.Methods and resultsSixty patients emergently hospitalized owing to CHF‐induced dyspnea were randomly assigned to receive either 40 mg intravenous furosemide daily or 7.5 mg oral tolvaptan for 5 days after admission. Both groups also received intravenous carperitide and canrenoate potassium. As results, baseline patient characteristics were similar between the furosemide (n = 30) and the tolvaptan (n = 30) groups, with no significant difference in 5 day urine volume or fluid balance. Brain natriuretic peptide and body weight improvements were similar between groups. However, serum creatinine (Cr) level did not increase, and the incidence of worsening renal function was significantly lower in the tolvaptan group. Consequently, the Cr increase to gain 1000 mL urine was 2.5‐fold lower in the tolvaptan group. Furthermore, the blood urea nitrogen (BUN)/Cr ratio significantly decreased in the tolvaptan group, suggesting that renal perfusion was preserved, and urea reuptake and passive water reabsorption were suppressed following tolvaptan treatment. Although catecholamine improvements after treatment were not significantly different, plasma renin activity was enhanced in the furosemide group.ConclusionsAs compared with furosemide, tolvaptan in patients with acute heart failure is associated with comparable decongestion, better preservation of renal function and less activation of renin–angiotensin system. (UMIN 000014134).

Effects of Additive Tolvaptan vs. Increased Furosemide on Heart Failure With Diuretic Resistance and Renal Impairment ― Results From the K-STAR Study ―

“…Previous studies of TLV use were tested in acute HF without accounting for diuretic resistance. [8][9][10][11] There are 3 main findings of the present study. First, additive TLV resulted in significantly higher UV than increased FUR, primarily through increased urinary water excretion in HF patients with residual congestion despite concomitant FUR.…”

Tolvaptan Reduces the Risk of Worsening Renal Function in Patients With Acute Decompensated Heart Failure and Preserved Left Ventricular Ejection Fraction ― Prospective Randomized Controlled Study ―

“…Furthermore, in the study by Jujo et al, in which the effects of oral tolvaptan and intravenous furosemide on renal response were directly compared in ADHF patients, the WRF rate was significantly lower in HFpEF patients treated with tolvaptan than in HFpEF patients treated with furosemide, although the subgroup of HFpEF patients was not prospectively defined. 33 Although we observed an increased risk of WRF in ADHF patients treated with conventional diuretic therapy, there might be transient WRF during the acute phase that is not necessarily associated with a worse prognosis. 34 According to recent reports, transient WRF seems to provide some prognostic information in ADHF, 7 but its effect seems to be less than that of persistent WRF.…”

New Insights Into Tolvaptan Treatment and the Renin-Angiotensin-Aldosterone System

“…4) Our recent pharmacokinetic and pharmacodynamic studies have reported the effectiveness and safety of add-on tolvaptan to furosemide in HF patients with advanced kidney dysfunction. 5,6) As compared with furosemide, tolvaptan in patients with acute HF is associated with comparable decongestion, better preservation of renal function, and less activation of the RAAS; 7) however, the efficacy of tolvaptan with or without ARB/ACE-I therapy in hospitalized patients with acute decompensated HF has not been fully investigated. The most recently published study of Adachi, et al 8) suggested that a single use of tolvaptan might induce an increase in urine volume in acute decompensated HF patients who were not previously treated with ARB/ACE-I.…”