Treatment of pulmonary arterial hypertension with bosentan: from pathophysiology to clinical evidence.

In addition to its potent vasoconstricting effect, endothelin (ET)-1 induces proliferation of pulmonary vascular cells and appears to play a pathogenic role in the development of pulmonary arterial hypertension (PAH). Blockade of the ET receptors has been proposed for the treatment of this condition. Bosentan (Tracleer, Actelion Pharmaceuticals), an oral ETA/ETB receptor antagonist, has been shown to improve exercise capacity, quality of life, haemodynamics and time to clinical worsening of patients with PAH in short-term placebo-controlled trials. These improvements were sustained, and a long-term observational study on idiopathic PAH patients suggested a favourable effect on survival in this subset. In the present report, the pharmacology, clinical efficacy and safety profile of bosentan are summarised. The place of bosentan among the current therapies available for the treatment of PAH is also discussed.