Ambrisentan for the treatment of pulmonary arterial hypertension

Correspondence: James R Klinger Division of Pulmonary Sleep and Critical Care Medicine, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903 Tel +1 401 444 2776 Fax +1 401 444 3002 Email [email protected] Abstract: Ambrisentan is an endothelin receptor antagonist (ERA) that was recently approved for treatment of pulmonary arterial hypertension (PAH). Endothelin (ET) is a potent vasoconstrictor with mitogenic, hypertrophic and pro-infl ammatory properties that is upregulated in pulmonary hypertensive diseases. The biologic effects of ET are mediated by 2 cell surface receptors termed ET A and ET B . ET A mediates the vasoconstrictor effect of ET on vascular smooth muscle, whereas ET B is expressed primarily on vascular endothelial cells where it induces nitric oxide synthesis and acts to clear ET from the circulation. Ambrisentan is the fi rst ET A selective ERA approved for use in the US. Recently published clinical trials in patients with PAH demonstrate improvement in functional capacity and pulmonary hemodynamics similar to other ET A selective and non-selective ERAs. Its once daily dosing and lower incidence of serum aminotransferase elevation offer potential advantages over other ERAs, but further experience with this agent is needed to fully understand its long-term effi cacy and safety. This review discusses the endothelin family of proteins and receptors and their role in the pathophysiology of pulmonary hypertensive diseases. It also examines the development process, safety profi le and clinical trials that have resulted in ambrisentan being approved for treatment of PAH.