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

Int J Cardiol. 2016 Oct 15:221:188-93. doi: 10.1016/j.ijcard.2016.07.063. Epub 2016 Jul 5.

Abstract

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 60mL/min/1.73m(2)) were randomized within 6h from hospitalization to either tolvaptan treatment for 2days or conventional treatment. The primary outcome was the combined endpoint of all-cause death and HF readmission.

Results: During follow-up (636days, 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 30mL/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.

Keywords: Acute heart failure; Neurohormonal activity; Prognosis; Renal dysfunction.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Aged
  • Antidiuretic Hormone Receptor Antagonists / administration & dosage
  • Antidiuretic Hormone Receptor Antagonists / adverse effects
  • Benzazepines* / administration & dosage
  • Benzazepines* / adverse effects
  • Comorbidity
  • Early Medical Intervention / methods
  • Female
  • Glomerular Filtration Rate
  • Heart Failure* / diagnosis
  • Heart Failure* / drug therapy
  • Heart Failure* / epidemiology
  • Hospitalization / statistics & numerical data
  • Humans
  • Kidney Function Tests / methods
  • Male
  • Middle Aged
  • Prognosis
  • Renal Insufficiency* / diagnosis
  • Renal Insufficiency* / epidemiology
  • Tolvaptan
  • Treatment Outcome

Substances

  • Antidiuretic Hormone Receptor Antagonists
  • Benzazepines
  • Tolvaptan