title: Hemodynamic and clinical effects of tezosentan, an intravenous dual endothelin receptor antagonist, in patients hospitalized for acute decompensated heart failure.
abstract: OBJECTIVE
  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.affiliation: Section of Cardiology, Methodist DeBakey Heart Center and Baylor College of Medicine, Texas Medical Center, One Baylor Plaza, Houston, TX 77030, USA. gtorre@bcm.tmc.edu
authors.forename: Guillermo
authors.initials: G
authors.lastname: Torre-Amione
authors.forename: James B
authors.initials: JB
authors.lastname: Young
authors.forename: Wilson S
authors.initials: WS
authors.lastname: Colucci
authors.forename: Basil S
authors.initials: BS
authors.lastname: Lewis
authors.forename: Craig
authors.initials: C
authors.lastname: Pratt
authors.forename: Gad
authors.initials: G
authors.lastname: Cotter
authors.forename: Karl
authors.initials: K
authors.lastname: Stangl
authors.forename: Uri
authors.initials: U
authors.lastname: Elkayam
authors.forename: John R
authors.initials: JR
authors.lastname: Teerlink
authors.forename: Aline
authors.initials: A
authors.lastname: Frey
authors.forename: Maurizio
authors.initials: M
authors.lastname: Rainisio
authors.forename: Isaac
authors.initials: I
authors.lastname: Kobrin
mesh_terms: D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D065128:Endothelin Receptor Antagonists; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D065128:Endothelin Receptor Antagonists; D011725:Pyridines; D013777:Tetrazoles; C120582:tezosentan