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