The medication tezosentan, which was thought could be beneficial for the treatment of acute heart failure, did not improve breathlessness or reduce the risk of fatal or nonfatal cardiovascular events, according to a study in the November 7 issue of JAMA.
Patients with heart failure have higher plasma concentrations of the vasoconstrictor peptide endothelin-1 (a peptide that can cause narrowing of a blood vessel opening), which has been associated with worse clinical or health outcomes, according to background information in the article. Tezosentan is an intravenous short-acting endothelin receptor antagonist (a drug that neutralizes or counteracts the effects of another drug) and a vasodilator (a drug that causes dilation of blood vessels).
John J. V. McMurray, M.D., of Western Infirmary, Glasgow, United Kingdom, and colleagues conducted the Value of Endothelin Receptor Inhibition With Tezosentan in Acute Heart Failure Studies (VERITAS) to test the hypothesis that tezosentan would have a favorable effect on symptoms and clinical outcomes in patients with acute heart failure. The two randomized trials were conducted from April 2003 through January 2005 at sites in Australia, Europe, Israel, and North America and included 1,435 patients admitted with certain heart failure symptoms. The patients were randomized to tezosentan (5 mg/hour for 30 minutes, followed by 1 mg/hour for 24 to 72 hours [n = 730]) or placebo (n = 718).
The researchers found that tezosentan did not improve dyspnea (difficulty breathing) more than placebo in either trial. The incidence of death or worsening heart failure at seven days in the combined trials was 26 percent in each treatment group, and up to 30 days was 32 percent in the tezosentan group and 33 percent in the placebo group. The number of deaths at six months was 104 (14.3 percent) in the tezosentan group and 101 (14.3 percent) in the placebo group.
“In summary, tezosentan, a treatment with ‘favorable' hemodynamic actions, failed to improve breathlessness or reduce fatal and nonfatal cardiovascular events in patients following an emergency admission to hospital with acute heart failure. So far, it has proved impossible to identify a therapeutic role for endothelin antagonists in patients with acute or chronic heart failure,” the authors write.