Hemodynamic and clinical effects of tezosentan, an intravenous dual endothelin
receptor antagonist, in patients hospitalized for acute decompensated heart
failure.
Author(s): Torre-Amione G(1), Young JB, Colucci WS, Lewis BS, Pratt C, Cotter G, Stangl K,
Elkayam U, Teerlink JR, Frey A, Rainisio M, Kobrin I.
Affiliation(s): Author information:
(1)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
Publication date & source: 2003, J Am Coll Cardiol. , 42(1):140-7
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.
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