R E V I E W Treprostinil for pulmonary hypertension Nika Skoro-Sajer1 Irene Lang1 Robert Naeije2 1Division of Cardiology, Department of Internal Medicione II, Vienna General Hospital, Medical University of Vienna, Austria; 2Department of Cardiology, Erasme University Hospital, Brussels, Belgium Correspondence: Robert Naeije Department of Pathophysiology, Erasme Campus, CP 604, 808, Lennik road, B-1070, Brussels, Belgium Tel +1 32 2 5553322 Fax +1 32 2 5554124 Email rnaeije@ulb.ac.be Abstract: Treprostinil is a stable, long-acting prostacyclin analogue which can be admin- istered as a continuous subcutaneous infusion using a portable miniature delivery system. Subcutaneous treprostinil has been shown in a large multicenter randomized controlled trial to improve exercise capacity, clinical state, functional class, pulmonary hemodynamics, and quality of life in patients with pulmonary arterial hypertension, an uncommon disease of poor prognosis. Side effects include facial ﬂush, headache, jaw pain, abdominal cramping, and diar- rhea, all typical of prostacyclin, and manageable by symptom-directed dose adjustments, and infusion site pain which may make further treatment impossible in 7%–10% of the patients. Long-term survival in pulmonary arterial hypertension patients treated with subcutaneous treprostinil is similar to that reported with intravenous epoprostenol. There are uncontrolled data suggesting efﬁcacy of subcutaneous treprostinil in chronic thromboembolic pulmonary hypertension. Treprostinil can also be administered intravenously, although increased doses, up to 2–3 times those given subcutaneously, appear to be needed to obtain the same efﬁcacy. Preliminary results of a randomized controlled trial of inhaled treprostinil on top of bosentan and sildenaﬁl therapies have shown signiﬁcance on the primary endpoint, which was exer- cise capacity as assessed by the distance walked in 6 minutes. Trials of oral formulations of treprostinil have been initiated. Keywords: pulmonary hypertension, prostacyclin, epoprostenol, treprostinil, congenital heart disease, connective tissue disease, portal hypertension, HIV infection, anorexigens Introduction Treprostinil is used to treat pulmonary arterial hypertension (PAH), which is a dyspnea-fatigue syndrome deﬁned by an isolated increase in pulmonary vascular resistance (PVR) leading to progressive right heart failure (Farber and Loscalzo 2004). In spite of remarkable advances achieved with the introduction of prostacyclins, endothelin receptor antagonists (ERA), and phosphodiesterase-5 (PDE-5) inhibitors (Humbert et al 2004), the prognosis of PAH remains unfavorable, with estimated medial life expectancies of 5–6 years, and insufﬁcient clinical improvement in about half of the survivors after 1–2 years (McLaughlin et al 2004; Provencher et al 2006). PAH occurs in association with a variety of conditions, which include connective tissue diseases (CTD), congenital heart diseases (CHD), portal hypertension, human immunodeﬁciency virus (HIV) infection, and intake of appetite-suppressant drugs, mainly fenﬂuramines (Simmoneau et al 2004). Recently reported incidences and prevalences of PAH range from 2.4 to 7.6 cases per million/year and 15 to 52 per million respectively (Humbert et al 2006; Peacock et al 2007). The diagnosis of PAH is based on a right heart catheterization to demonstrate a mean pulmonary artery pressure (Ppa) higher than 25 mmHg at rest and 30 mmHg at exercise, a normal left atrial pressure, estimated by a pulmonary artery wedge pressure (Ppw) of less than 15 mmHg, a PVR of more than 240 dyne.s.cm–5, and a systematic work-up to exclude left heart failure with increased pulmonary venous pressure, respira- tory diseases and/or hypoxemia, and chronic thromboembolic pulmonary hypertension (CTEPH) (Galie et al 2004; Badesch et al 2007). Vascular Health and Risk Management 2008:4(3) 507–513 © 2008 Dove Medical Press Limited. All rights reserved 507