Furosemide As A Factor To Deteriorate Therapeutic Efficacy Of Tolvaptan In Patients With Decompensated Cirrhosis

Aim To optimize the therapeutic strategy for patients with decompensated cirrhosis manifesting hepatic ascites and/or edema, factors affecting the outcome of patients receiving tolvaptan were evaluated. Methods The subjects were 165 patients receiving tolvaptan including 116 patients (70%) also treated with furosemide. The therapeutic efficacy of tolvaptan was defined as "effective" when a body weight reduction of 1.5 kg or more was obtained within 1 week. The long-term outcome was defined as "favorable" when the ascites-related events-free duration was prolonged following tolvaptan treatment, compared with that before treatment, or ascites-related events were absent for at least 120 days during treatment based on the hazard function analysis. Results Tolvaptan was effective in 115 patients (70%). Among them, the long-term outcome was evaluated in 99 patients and was favorable in 70 patients (71%). A multivariate analysis revealed that the serum blood urea nitrogen levels at baseline (odds ratio 0.960 per +1 mg/dL,P = 0.021) and the type of tolvaptan initiation (planned vs. emergent; 3.695,P < 0.001) were associated with therapeutic efficacy, while the furosemide dose (0.280 per +20 mg/day,P = 0.014) and previous ascites-related events (0.074,P < 0.001) were associated with the long-term outcome. Receiver operating curve analyses identified the optimal cut-off values for the furosemide dose as 15 mg/day (P < 0.001). Furthermore, the cumulative survival rates in patients receiving furosemide at 15 mg/day or less were significantly higher than those in the remaining patients (P = 0.048). Conclusion Furosemide given at baseline contributed to an unfavorable outcome in patients receiving tolvaptan; consequently, tolvaptan should be given before increasing the furosemide dose.