Current treatment options in children with pulmonary arterial hypertension and experiences with oral bosentan

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by vasoconstriction and progressive remodelling of the pulmonary arterial wall leading to right ventricular failure and death. Idiopathic PAH (IPAH) and PAH associated with congenital heart defects account for the majority of paediatric patients with PAH. During the last few decades, several pharmacological approaches have been introduced, including calcium channel-blockers (CCBs), prostacyclin analogues, endothelin receptor antagonists and, most recently, phosphodiesterase inhibitors. This paper reviews the treatment options available to children with a special focus on the initial experience with bosentan. Although CCBs have been shown to increase survival in IPAH, the beneficial effect appears to be limited to a small number of patients, defined as 'responders' to the vasoreactivity testing. With the availability of prostacyclin (intravenous epoprostenol) and then prostacyclin analogues, the treatment options have increased markedly and particularly in patients who have not responded to conventional therapy. Although epoprostenol has been shown to be efficacious in PAH, the drug is not ideal owing to serious complications arising from the invasive mode of application, particularly in children. Phosphodiesterase-5 inhibitors have also shown beneficial effects. Targeting the endothelin (ET) system with the oral, dual ET(A)/ET(B) receptor antagonist, bosentan has been demonstrated to improve the cardiopulmonary haemodynamics, exercise capacity, quality-of-life and survival in adult patients with PAH. Specific ET(A) antagonists may also present the same beneficial profile. Recent experience with bosentan in paediatric patients with PAH indicates that the results obtained in adult patients may be extrapolated to children, thus offering a safe and effective therapy that is easy to administer.