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

JAMA. 2007 Nov 7;298(17):2009-19. doi: 10.1001/jama.298.17.2009.


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).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Aged
  • Cardiac Output
  • Double-Blind Method
  • Dyspnea
  • Endothelin Receptor Antagonists*
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / metabolism
  • Heart Failure / physiopathology
  • Humans
  • Infusions, Intravenous
  • Male
  • Pulmonary Wedge Pressure
  • Pyridines / therapeutic use*
  • Tetrazoles / therapeutic use*
  • Treatment Outcome
  • Vascular Resistance
  • Vasodilator Agents / therapeutic use*


  • Endothelin Receptor Antagonists
  • Pyridines
  • Tetrazoles
  • Vasodilator Agents
  • tezosentan

Associated data

  • ClinicalTrials.gov/NCT00524433
  • ClinicalTrials.gov/NCT00525707