Effects of Tolvaptan Addition to Furosemide in Normo- and Hyponatremia Patients with Heart Failure and Chronic Kidney Disease Stages G3b-5: A Subanalysis of the K-STAR Study

Background: Tolvaptan increases free water clearance (aquaresis) and thereby improves hyponatremia. Although hyponatremia on admission is common in patients with congestive heart failure (CHF), little is known regarding the response to tolvaptan in those who also have chronic kidney disease (CKD) with or without hyponatremia. The aim of this subanalysis was to investigate the differences in treatment response between normo- and hyponatremia patients with CHF and CKD stages G3b-5. Methods: The Kanagawa Aquaresis Investigators Trial of Tolvaptan on HF Patients with Renal Impairment (K-STAR) was a multicenter, open-label, randomized, controlled prospective clinical trial that included 81 Japanese patients with CHF and residual signs of congestion despite oral furosemide treatment (≥40 mg/day). All patients were randomly assigned to 7-day treatment with either ≤15 mg/day of new add-on tolvaptan or ≤40 mg/day of increased furosemide. A subanalysis was conducted for 73 patients, who were classified into 2 groups according to their assigned treatment, then further stratified into 2 subgroups according to their serum sodium concentration [Na + ]. The differences between the urine and serum parameters from day 1 to 3 were compared between the groups and between the subgroups in each group. Results: The change (Δ) in urine volume (ΔUV) and Δurine osmolality were greater in the tolvaptan group than in the furosemide group; however, ΔUV and Δurine osmolality did not show significant differences between the normonatremia subgroup and the hyponatremia subgroup in each group. In addition, Δserum [Na + ] was greater in the tolvaptan group, although the change was not clinically significant. In contrast, Δserum [Na + ] did not show significant differences between the normo- and hyponatremia subgroups in each group. Conclusion: Tolvaptan added to furosemide resulted in a greater diuretic effect than increased furosemide, even in normonatremia patients with CHF complicated by CKD stages G3b-5 in the very early treatment phase.