Effects of tezosentan on symptoms and clinical outcomes in patients with acute
heart failure: the VERITAS randomized controlled trials.
Author(s): McMurray JJ(1), Teerlink JR, Cotter G, Bourge RC, Cleland JG, Jondeau G, Krum H,
Metra M, O'Connor CM, Parker JD, Torre-Amione G, van Veldhuisen DJ, Lewsey J,
Frey A, Rainisio M, Kobrin I; VERITAS Investigators.
Affiliation(s): Author information:
(1)Department of Cardiology, Western Infirmary, Glasgow, G12 8QQ, United Kingdom.
j.mcmurray@bio.gla.ac.uk
Publication date & source: 2007, JAMA. , 298(17):2009-19
CONTEXT: Plasma concentrations of the vasoconstrictor peptide endothelin-1 are
increased in patients with heart failure, and higher concentrations are
associated with worse outcomes. Tezosentan is an intravenous short-acting
endothelin receptor antagonist that has favorable hemodynamic actions in heart
failure.
OBJECTIVE: To determine if tezosentan improves outcomes in patients with acute
heart failure.
DESIGN, SETTING, AND PARTICIPANTS: The Value of Endothelin Receptor Inhibition
With Tezosentan in Acute Heart Failure Studies, 2 independent, identical, and
concurrent randomized, double-blind, placebo-controlled, parallel-group trials
conducted from April 2003 through January 2005 at sites in Australia, Europe,
Israel, and North America. Patients admitted within the previous 24 hours with
persisting dyspnea and a respiratory rate of 24/min or greater were eligible
provided they fulfilled 2 of 4 criteria: (1) elevated plasma concentrations of
B-type or N-terminal pro-B-type natriuretic peptide, (2) clinical pulmonary
edema, (3) radiologic pulmonary congestion or edema, or (4) left ventricular
systolic dysfunction.
INTERVENTION: Infusion of tezosentan (5 mg/h for 30 minutes, followed by 1 mg/h
for 24 to 72 hours [n = 730]) or placebo (n = 718).
MAIN OUTCOME MEASURES: The coprimary end points were change in dyspnea (measured
at 3, 6, and 24 hours using a visual analog scale from 0-100) over 24 hours (as
area under the curve) in the individual trials and incidence of death or
worsening heart failure at 7 days in both trials combined.
RESULTS: Of the 1435 patients who received treatment as assigned, 855 (60%) were
men; mean age was 70 years. Mean left ventricular ejection fraction (measured in
779 patients [54%]) was 29% (SD, 11%). Baseline dyspnea scores were similar in
the 2 treatment groups. Tezosentan did not improve dyspnea more than placebo in
either trial, with a mean treatment difference of -12 (95% confidence interval
[CI], -105 to 81) mm . h (P = .80) in the first trial and -25 (95% CI, -119 to
69) mm x h (P = .60) in the second. The incidence of death or worsening heart
failure at 7 days in the combined trials was 26% in each treatment group (odds
ratio, 0.99; 95% confidence interval, 0.82-1.21; P = .95).
CONCLUSION: The endothelin receptor antagonist tezosentan did not improve
symptoms or clinical outcomes in patients with acute heart failure.
TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT00525707 (VERITAS-1) and
NCT00524433 (VERITAS-2).
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