Prognostic impact of early treatment with tolvaptan in patients with acute heart failure and renal dysfunction

Background: Renal dysfunction is a common comorbidity in acute heart failure (AHF) patients. The prognostic significance of early treatment with tolvaptan in AHF patients complicated with renal dysfunction has not been elucidated. Methods: Post hoc analysis was performed on a randomized clinical study for prespecified prognostic endpoints and prespecified subgroups. 217 AHF patients with renal dysfunction (eGFR 15 to 60 mL/min/1.73 m(2)) were randomized within 6 h from hospitalization to either tolvaptan treatment for 2 days or conventional treatment. The primary outcome was the combined endpoint of all-cause death and HF readmission. Results: During follow-up (636 days, median) 99 patients experienced combined endpoint and 53 patients died. There was no significant difference in event-free survival rate for either the combined events (Log-rank: P = 0.197) or all-cause death (Log-rank: P=0.894) between tolvaptan and conventional groups. In prespecified subgroup analysis, in patients whose BUN/creatinine ratio was above the median (>20), tolvaptan significantly reduced the risk of combined events (HR: 0.52, 95% CI: 0.30-0.91, P = 0.021) with a significant interaction (P value for interaction = 0.045). Likewise, in patients whose eGFR was 30 mL/min/1.73m(2) or above, tolvaptan reduced the risk of combined events (HR: 0.54, 95% CI: 0.32-0.90, P = 0.017) with a significant interaction (P value for interaction = 0.015). Conclusion: Short-term use of tolvaptan in acute-phase in AHF with renal dysfunction showed a neutral effect on prognosis. Patients with relatively preserved renal function and relatively high BUN/creatinine ratios are potentially favorable subgroups for treatment with tolvaptan. (C) 2016 Elsevier Ireland Ltd. All rights reserved.