Effects of tezosentan on symptoms and clinical outcomes in patients with acute heart failure: the VERITAS Randomized controlled trials

McMurray, J.J.V. et al. (2007) Effects of tezosentan on symptoms and clinical outcomes in patients with acute heart failure: the VERITAS Randomized controlled trials. JAMA: Journal of the American Medical Association, 298(17), pp. 2009-2019. (doi:10.1001/jama.298.17.2009)

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Publisher's URL: http://dx.doi.org/10.1001/jama.298.17.2009

Abstract

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 · 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lewsey, Professor Jim and McMurray, Professor John
Authors: McMurray, J.J.V., Teerlink, J.R., Cotter, G., Bourge, R.C., Cleland, J.G.F., Jondeau, G., Krum, H., Metra, M., O'Connor, C.M., Parker, J.D., Torre-Amione, G., van Veldhuisen, D.J., Lewsey, J., Frey, A., Rainisio, M., and Kobrin, I.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Health Economics and Health Technology Assessment
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Centre for Population and Health Sciences
Journal Name:JAMA: Journal of the American Medical Association
ISSN:0098-7484
ISSN (Online):1538-3598

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