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

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: Guillermo Torre-Amione, James B Young, Wilson S Colucci, Basil S Lewis, Craig Pratt, Gad Cotter, Karl Stangl, Uri Elkayam, John R Teerlink, Aline Frey, Maurizio Rainisio, Isaac Kobrin
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 42 Issue 1 Pg. 140-7 (Jul 02 2003) ISSN: 0735-1097 [Print] United States
• PMID: 12849674 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Endothelin Receptor Antagonists
• Pyridines
• Tetrazoles
• tezosentan

Topics

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