Tezosentan in patients with acute heart failure and acute coronary syndromes:
results of the Randomized Intravenous TeZosentan Study (RITZ-4).
Author(s): O'Connor CM(1), Gattis WA, Adams KF Jr, Hasselblad V, Chandler B, Frey A, Kobrin
I, Rainisio M, Shah MR, Teerlink J, Gheorghiade M; Randomized Intravenous
TeZosentan Study-4 Investigators.
Affiliation(s): Author information:
(1)Duke University Medical Center and Duke Clinical Research Institute, Durham,
North Carolina 27705, USA.
Publication date & source: 2003, J Am Coll Cardiol. , 41(9):1452-7
OBJECTIVES: We sought to determine the effect of tezosentan in patients with
acute decompensated heart failure (HF) associated with acute coronary syndrome
(ACS).
BACKGROUND: Tezosentan is a dual endothelin receptor antagonist that has been
shown to improve cardiac output, decrease pulmonary capillary wedge pressure, and
reduce pulmonary and systemic vascular resistance in initial clinical studies in
acute decompensated HF.
METHODS: The Randomized Intravenous TeZosentan (RITZ)-4 study was a multicenter,
randomized, double-blinded, placebo-controlled study of tezosentan in patients
with acute decompensated HF associated with ACS. A total of 193 patients were
randomized to receive tezosentan (25 mg/h for 1 h, then 50 mg/h for 23 to 47 h)
or placebo. Patients with evidence of acute decompensated HF and ACS were
eligible to participate. The primary end point was the composite of death,
worsening HF, recurrent ischemia, and recurrent or new myocardial infarction
within 72 h.
RESULTS: No significant differences were observed between placebo and 50 mg/h
tezosentan in the composite primary end point: 24.2% (95% confidence interval
[CI] 16.0% to 34.1%) and 28.9% (95% CI 20.1% to 39.0%), respectively (p =
0.5152). Symptomatic hypotension was more frequent in the treatment group.
CONCLUSIONS: At the doses studied, tezosentan did not result in a significant
improvement in the composite primary clinical end point in the RITZ-4 trial.
Tezosentan did not demonstrate pro-ischemic effects in this population.
Symptomatic hypotension may have resulted in an increased number of adverse
events in the treatment group. Further studies with lower tezosentan doses are
warranted.
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