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Expert opinion on available options treating pulmonary arterial hypertension.

Naeije R, Huez S

Erasme University Hospital, Department of Pathophysiology, Erasme Campus, CP 604, 808, Lennik Road, B-1070 Brussels , Belgium. rnaeije@ulb.ac.be

Until in the early nineties, pulmonary arterial hypertension (PAH) was a uniformly fatal disease, with a median life expectancy of approximately 2.5 years. Uncontrolled studies showed that a small proportion of patients responded to high-dose calcium channel blockers, retrospective studies supported the use of anticoagulant therapy and heart-lung or lung transplantation remained the only option. In 1996, a 3-month randomised, placebo-controlled trial showed that chronic intravenous epoprostenol (synthetic prostacyclin) improved functional state, exercise capacity, haemodynamics, and even survival in patients with idiopathic PAH. Similar benefits were subsequently reported and extended to all PAH categories, and confirmed with more stable prostacyclin analogues administered subcutaneously (treprostinil), by inhalation (iloprost), or even orally (beraprost). In the early 2000s, two randomised controlled trials showed efficacy of the oral intake of the dual endothelin A/B receptor antagonist bosentan. Two selective endothelin-A receptor antagonists, sitaxsentan and ambrisentan, are being developed. Finally, a randomised controlled trial has established the therapeutic efficacy of phosphodiesterase-5 inhibition with sildenafil, introducing a third signalling pathway to be targeted by the pharmacological treatment of PAH. Another phosphodiesterase-5 inhibitor, tadalafil, is already being evaluated. While all these treatments have markedly improved the lives of PAH patients, they have not offered yet a cure of the disease. Multi-drug approaches are now under evaluation, with more ambitious therapeutic goals. Alternative approaches with stem cells, RhoA-Rho-kinase inhibitors, platelet derived growth factor inhibitors and vasoactive intestinal peptides are being considered.

Published 11 October 2007 in Expert Opin Pharmacother, 8(14): 2247-65.
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