Tezosentan Does Not Seem To Improve Outcomes Or Symptoms For People With Acute Heart Failure

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Main Category: Cardiovascular / Cardiology
Also Included In: Clinical Trials / Drug Trials
Article Date: 08 Nov 2007 - 8:00 PDT

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It was thought that tezosentan would benefit in the treatment of acute heart failure. However, it has been found that tezosentan does not reduce fatal or non-fatal cardiovascular events, neither does it help with breathlessness, according to an article published in the Journal of the American Medical Association (JAMA), November 7th issue.

People with heart failure have elevated plasma concentrations of vasoconstrictor peptide endothelin-1. Vasoconstrictor peptide endothelin-1 causes the narrowing of a blood vessel opening. These elevated plasma concentrations are linked to worse clinical or health outcomes, explain the authors.

Tezosentan is meant to neutralize the effects of another drug - it is a short-acting endothelin receptor antagonist. Tezosentan is also a drug that makes the blood vessels dilate (become broader, expand) - it is a vasodilator.

John J. V. McMurray, M.D., of Western Infirmary, Glasgow, United Kingdom, and team carried out the Value of Endothelin Receptor Inhibition With Tezosentan in Acute Heart Failure Studies (VERITAS) to find out whether tezosentan might have a beneficial effect on symptoms and clinical outcomes in acute heart failure patients. Two randomized trials were done, from April 2003 to January 2005 in Europe, North American and Israel. The trials involved 1,435 patients who had been admitted with specific heart failure symptoms. 730 of them were randomly selected to receive tezosentan (5 mg/hour for 30 minutes, followed by 1 mg/hour for 24 to 72 hours, while the other 718 received a placebo.

According to the researchers, those on tezosentan experienced no improvement with their breathing difficulties (dyspnea), compared to the placebo group. The number of deaths or cases of worsening heart failure at seven days in the combined trials was 26% in each treatment group, and after 30 days was 32% in the tezosentan group and 33% in the placebo group. 104 (14.3%) of patients had died after six months in the tezosentan group, compared to 101 (14.3%) in the placebo group.

The researchers wrote "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."

"Effects of Tezosentan on Symptoms and Clinical Outcomes in Patients With Acute Heart Failure"
The VERITAS Randomized Controlled Trials
John J. V. McMurray, MD; John R. Teerlink, MD; Gadi Cotter, MD; Robert C. Bourge, MD; John G. F. Cleland, MD; Guillaume Jondeau, MD; Henry Krum, MD; Marco Metra, MD; Christopher M. O'Connor, MD; John D. Parker, MD; Guillermo Torre-Amione, MD, PhD; Dirk J. van Veldhuisen, MD; Jim Lewsey, PhD; Aline Frey, PharmD; Maurizio Rainisio, PhD; Isaac Kobrin, MD; for the VERITAS Investigators
JAMA. 2007;298(17):2009-2019.
Click here to view abstract online

Written by׃ Christian Nordqvist
Copyright: Medical News Today
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