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Endothelin-1 is a vasoconstrictive peptide found in elevated concentrations in patients with acute heart failure (HF), especially those with poor outcomes. An endothelin receptor antagonist, tezosentan, improved hemodynamic measures in small trials in patients with acute HF, prompting a pair of identical, international, controlled trials.
Patients (1435; mean age, 70) had acute left ventricular failure and dyspnea (mean ejection fraction of 29%); those with cardiogenic shock, acute myocardial infarction, renal failure, or other more critical complications were excluded. Patients were randomized to 24–72 hour infusions of tezosentan or placebo. Despite significant improvements among treated subjects in pulmonary capillary wedge pressure, mean…