Hemodynamic and clinical effects of tezosentan, an intravenous dual endothelin receptor antagonist, in patients hospitalized for acute decompensated heart failure. Academic Article uri icon

Overview

abstract

  • OBJECTIVES: We sought to investigate the efficacy and safety of tezosentan, a dual endothelin receptor antagonist, in patients hospitalized for acute heart failure (HF). BACKGROUND: Tezosentan has been previously shown to improve hemodynamics in patients with stable chronic HF. METHODS: In a double-blind fashion, 292 patients (cardiac index < or =2.5 l/min per m(2) and pulmonary capillary wedge pressure (PCWP) > or =15 mm Hg) who were admitted to the hospital and in need of intravenous treatment for acute HF and central hemodynamic monitoring were randomized to 24-h intravenous treatment with tezosentan (50 or 100 mg/h) or placebo. Central hemodynamic variables, the dyspnea score, and safety variables were measured. RESULTS: After 6 h of treatment, significantly greater increases in the cardiac index and decreases in PCWP were observed with both tezosentan dosages than with placebo (mean treatment effects at 0.38 and 0.37 l/min per m(2) with 50 and 100 mg/h and -3.9 mm Hg for each dose, respectively; p < 0.0001). This effect was maintained during the remaining infusion and for > or =6 h after treatment cessation. A tendency for an improved dyspnea score and a decreased risk of clinical worsening was observed after 24 h of treatment with each tezosentan dose. Adverse events, more frequent with tezosentan than with placebo (headache, asymptomatic hypotension, early worsening of renal function, nausea, vomiting), were dose-related. CONCLUSIONS: Intravenous tezosentan rapidly and effectively improved hemodynamics in these patients. The similar beneficial effects of the two dosages and the increased dose-related adverse events with the higher dosage suggest that the optimal dosing regimen is <50 mg/h.

authors

  • Torre Amione, Guillermo
  • Young, James B
  • Colucci, Wilson S
  • Lewis, Basil S
  • Pratt, Craig
  • Cotter, Gad
  • Stangl, Karl
  • Elkayam, Uri
  • Teerlink, John R
  • Frey, Aline
  • Rainisio, Maurizio
  • Kobrin, Isaac

publication date

  • July 2, 2003

Research

keywords

  • Endothelin Receptor Antagonists
  • Heart Failure
  • Pyridines
  • Tetrazoles

Identity

Scopus Document Identifier

  • 0037868058

Digital Object Identifier (DOI)

  • 10.1016/s0735-1097(03)00556-4

PubMed ID

  • 12849674

Additional Document Info

volume

  • 42

issue

  • 1