Endothelin receptor antagonists for the treatment of pulmonary artery hypertension

AIMS: The demonstration that endothelin production is upregulated in pulmonary artery hypertension (PAH) served as the rationale for developing endothelin-receptor antagonists (ERAs) as a treatment for PAH. This article reviews the primary studies demonstrating efficacy of ERAs in PAH. MAIN METHODS: Multicenter, placebo-controlled trials and open-label extension studies. KEY FINDINGS: Two orally active ERAs are currently approved for the treatment of PAH - the dual receptor antagonist bosentan, and the more selective ET(A) receptor antagonist ambrisentan-based on multicenter randomized clinical trials demonstrating efficacy and safety. Long-term experience with both agents supports maintenance of therapeutic effects in most patients. Adverse effects, including altered liver function and edema may occur and require careful monitoring. SIGNIFICANCE: Despite failure to demonstrate efficacy of ERAs in other cardiopulmonary conditions, ERAs have a major role in the treatment algorithm for PAH.