Association between plasma concentration of tolvaptan and urine volume in acute decompensated heart failure patients with fluid overload

Background: Tolvaptan (TLV) is a useful diuretic for acute decompensated heart failure (ADHF) with fluid overload, but its clinical response varies between patients. The aim of this study is to investigate whether plasma TLV concentrations correlate with the urine volume. Methods: ADHF inpatients with evidence of fluid overload and total urine volume < 1,500 mL 24 h after initial intravenous administration of 40 mg furosemide were included in the study. On days 1–7, 7.5 mg oral TLV was added. The plasma TLV concentration, plasma renin activity (PRA), and plasma aldosterone concentration (PAC) were measured on days 1, 3 and 7. Results: In the 52 patients who completed the protocol, the TLV concentration increased significantly from 67.6 ± 30.1 ng/mL on day 1 to 98.3 ± 39.6 ng/mL on day 3 to 144.8 ± 44.2 ng/mL on day 7, and the TLV concentration correlated with total urine volume on days 3 and 7 (r = 0.392, p < 0.01; r = 0.639, p < 0.001, respectively) but not on day 1. The urine volume correlated inversely with PRA and PAC (r = −0.618, p < 0.05; r = −0.547, p < 0.05, respectively). Conclusions: Plasma TLV concentrations correlated with the urine volume in late phase of treatment but not in early phase, which suggests that the effect of TLV may possibly be inhibited by renin–angiotensin–aldosterone system activity.

Clinical effects of adding tolvaptan to intravenous furosemide in patients with congestive heart failure

Background: Tolvaptan, a vasopressin V2 receptor antagonist, is a strong diuretic with a new mechanism of action and has good adaptation to patients with congestive heart failure. Knowledge on the proper use of furosemide, an existing therapeutic drug, is not yet sufficient. Objectives: Clinical differences when 7.5 mg of tolvaptan was added to the usual furosemide therapy were examined. Materials and Methods: Patients who required hospitalization for congestive heart failure were randomly assigned to a group treated for 7 days with furosemide alone (FRO group) and a group treated with furosemide plus tolvaptan (TLV group) for 7 days and examined for symptoms. Physical examinations were performed every day, and blood testing, including N-terminal pro-brain natriuretic peptide (NT-proBNP) level, plasma renin activity (PRA), plasma aldosterone concentration (PAC), and noradrenaline (NAD) level, was performed on days 1, 3, and 7. Results: FRO and TLV groups consisted of 51 (age, 66.4 ± 11.8 years, 62% of males) and 47 patients (67.9 ± 14.5 years, 64% of males), respectively. During the study, the TLV group had higher urine volume and decreased blood pressure due to the suppressed diuretic effect. The two groups showed significant differences in the degree of improvement of the jugular venous pressure (FRO vs. TLV groups: 6.3 ± 1.6 vs. 7.6 ± 2.5 cmH2O, P < 0.001, on day 3) and other physical findings. Although no significant differences in NT-proBNP and NAD levels were found, there were significant differences in PRA (19.8 ± 12.9 vs. 11.8 ± 8.0 ng/[mL . h], P < 0.001, on day 3) and PAC (FRO vs. TLV groups: 180.4 ± 148.4 vs. 124.7 ± 95.5 ng/mL, P < 0.01 on day 3 and 79.4 ± 73.9 vs. 56.8 ± 38.2 ng/mL, P < 0.05 on day 7). Conclusion: Adding 7.5 mg of tolvaptan to existing treatments with furosemide resulted in differences in clinical findings and neurohormonal factors, even though the degree of improvement in congestive heart failure was the same