Tezosentan in patients with acute heart failure and acute coronary syndromes: results of the Randomized Intravenous TeZosentan Study (RITZ-4).
OBJECTIVE
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.
O'Connor
Christopher M
CM
Duke University Medical Center and Duke Clinical Research Institute, Durham, North Carolina 27705, USA.
Gattis
Wendy A
WA
Adams
Kirkwood F
KF
Hasselblad
Vic
V
Chandler
Bleakley
B
Frey
Aline
A
Kobrin
Isaac
I
Rainisio
Maurizio
M
Shah
Monica R
MR
Teerlink
John
J
Gheorghiade
Mihai
M
D000208:Acute Disease; D000368:Aged; D003327:Coronary Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010865:Pilot Projects; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D013577:Syndrome; D013777:Tetrazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*
D011725:Pyridines; D013777:Tetrazoles; D014665:Vasodilator Agents; C120582:tezosentan