Tezosentan - A new endothelin receptor inhibitor for the treatment of congestive heart failure
Tumor Necrosis Factor-alpha
The endothelin (ET) receptor antagonist bosentan is the first member of this therapeutic class to have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of congestive heart failure (CHF). A new, highly potent non-selective ET inhibitor, tezosentan, has demonstrated the ability to improve cardiac index (CI) and other hemodynamic parameters in patients with decompensated heart failure, as well as the potential for improving diastolic function. Tezosentan has been evaluated in a series of placebo-controlled multicenter trials, the Randomized Intravenous TeZosentan (RITZ) studies. In the RITZ-1 and RITZ-2 trials, side effects associated with significant vasodilatation (hypotension and renal impairment) occurred, likely due to the use of dosage levels of tezosentan that were higher than necessary. However, improvement in both CI and pulmonary capillary wedge pressure (PCWP) were observed in RITZ-2. Based on clinical experience to date, a new double-blind, randomized placebo-controlled trial, VERITAS (Value of Endothelin Receptor Inhibition with Tezosentan in Acute Heart Failure), has been designed and is currently underway. It is hoped that this study and others will confirm that tezosentan has the potential attributes of the ideal therapeutic agent for CHF - the ability to substantially improve hemodynamics without significantly affecting ischemic burden or arrhythmogenicity, and with a high tolerability profile. Pending confirmation of the most appropriate dosage level of tezosentan for optimal efficacy and safety, and establishment of more specific patient selection criteria, results of studies with this investigative agent appear promising particularly with regard to treating pulmonary hypertension.