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Prostacyclin therapies for the treatment of pulmonary arterial hypertension

¹ Dept of Cardiology, University of Chicago Hospitals, Chicago, IL, USA, ² Dept of Pulmonology, Medical University Graz, Graz, Austria.

CORRESPONDENCE: H. Olschewski, Dept of Pulmonology, Medical University Graz, Auenbruggerplatz 20, Graz 8010, Austria, Fax: 43 3163853578. E-mail: horst.olschewski{at}meduni-graz.at

Keywords: Cor pulmonale, inhaled drugs, 6-min walk distance, prostacyclin, pulmonary circulation, vascular remodelling

Received: July 31, 2007
Accepted November 26, 2007

Prostacyclin and its analogues (prostanoids) are potent vasodilators and possess antithrombotic, antiproliferative and anti-inflammatory properties. Pulmonary hypertension (PH) is associated with vasoconstriction, thrombosis and proliferation, and the lack of endogenous prostacyclin may considerably contribute to this condition. This supports a strong rationale for prostanoid use as therapy for this disease. The first experiences of prostanoid therapy in PH patients were published in 1980.

Epoprostenol, a synthetic analogue of prostacyclin, and the chemically stable analogues iloprost, beraprost and treprostinil were tested in randomised controlled trials. The biological actions are mainly mediated by activation of specific receptors of the target cells; however, new data suggest effects on additional intracellular pathways. In the USA and some European countries, intravenous infusion of epoprostenol and treprostinil, as well as subcutaneous infusion of treprostinil and inhalation of iloprost, have been approved for therapy of pulmonary arterial hypertension. Iloprost infusion and beraprost tablets have been approved in few other countries. Ongoing clinical studies investigate oral treprostinil, inhaled treprostinil and the combination of inhaled iloprost and sildenafil in pulmonary arterial hypertension. Combination of other targeted therapies with prostanoids appears to be effective and safe.

After 25 yrs of continued knowledge, prostanoids remain a mainstay in the treatment of pulmonary arterial hypertension.

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