Dual endothelin receptor antagonism: setting standards in PAH

Endothelin (ET) has emerged as a key mediator in the pathophysiology of pulmonary arterial hypertension (PAH). The effects of ET are mediated by its binding to two receptors on endothelial and pulmonary smooth muscle cells: ET A and ET B . Blockade of both these receptors with the oral dual ET receptor antagonist, bosentan, represents an attractive treatment option for these severely compromised patients. The efficacy of bosentan in PAH has been demonstrated in randomised controlled trials in idiopathic PAH, and PAH associated with connective tissue diseases and congenital heart disease. In addition, an open-label study has shown clinical and haemodynamic effects in PAH associated with HIV infection. In these trials, bosentan has been shown to improve haemodynamics, increase functional capacity, improve time to clinical worsening, which is a surrogate marker of survival, and to improve patients' quality of life; in longer-term studies, it has been shown to improve patient outcome. The current article will present these key data from randomised controlled trials on bosentan as well as experiences from everyday clinical practice.