Furosemide Dose Changes Associated with Furosemide/Tolvaptan Combination Therapy in Patients with Cirrhosis

Abstract

Background: Few data have demonstrated that the combination therapy comprising a natriuretic drug and an aquaretic drug has improved renal function compared with the conventional diuretic therapy of only a natriuretic drug in patients with cirrhosis. Objective: This study aimed to assess the influence to the renal function by furosemide dose reductions after administration of tolvaptan in cirrhotic ascites patients. Methods: A 2-center, open-label, randomized study with a 24-week treatment period was conducted in Japan. Patients who met the study’s criteria were randomized to a conventional therapy group or a combination therapy group in a 1:1 ratio. The combination therapy group received tolvaptan and reduced furosemide doses compared with those received before the study enrollment. The conventional therapy group continued with the original dosage regimens. We assessed the change in estimated glomerular filtration rate (eGFR) from baseline through the duration of the study in the 2 groups. Results: Twenty-nine patients were randomized to receive either the combination therapy group (n = 14) or the conventional therapy group (n= 15). The change in the furosemide dose from baseline was –35.2 ± 10.1 mg in the combination therapy group. After 24 weeks of treatment, significantly greater improvement in eGFR was observed in the combination therapy group (2.4 ± 0.4 mL/min 1.73 m2) compared with those in the conventional therapy group (–5.1 ± 1.2 mL/min 1.73 m2; p = 0.013). Conclusion: A combination therapy of tolvaptan and furosemide enabled furosemide dose reductions. Systematic reductions of the furosemide doses can lead to the improvement of renal function.