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

J Am Coll Cardiol. 2003 Jul 2;42(1):140-7. doi: 10.1016/s0735-1097(03)00556-4.


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Endothelin Receptor Antagonists*
  • Female
  • Heart Failure / drug therapy
  • Heart Failure / physiopathology*
  • Hemodynamics / drug effects
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Pulmonary Wedge Pressure / drug effects
  • Pyridines / administration & dosage
  • Pyridines / pharmacology*
  • Pyridines / therapeutic use
  • Tetrazoles / administration & dosage
  • Tetrazoles / pharmacology*
  • Tetrazoles / therapeutic use


  • Endothelin Receptor Antagonists
  • Pyridines
  • Tetrazoles
  • tezosentan