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.