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How has epoprostenol changed the outcome for patients with pulmonary arterial hypertension?

Author(s): Barst R(1).

Affiliation(s): Author information: (1)Department of Pediatric Cardiology, Columbia University Medical Center, Scarsdale, NY 10583, USA. robyn.barst@gmail.com

Publication date & source: 2010, Int J Clin Pract Suppl. , (168):23-32

AIMS: Pulmonary arterial hypertension (PAH), characterized by increased pulmonary vascular resistance and pulmonary artery pressure, is a significant cause of morbidity and mortality in children and adults. Prior to 1995, there were no approved therapies for PAH. MATERIALS AND METHODS: Review of the clinical drug development of epoprostenol (synthetic prostacyclin) for the treatment of PAH. RESULTS: Based on the results of a phase 2 and one phase 3 trial carried out between 1987 and 1992 in adult patients with PAH, epoprostenol was approved for the treatment of severe idiopathic PAH in 1995. Continuous intravenous infusion 24/7 of epoprotenol improved exercise capacity, hemodynamic parameters, functional capacity and survival. Epoprostenol was subsequently shown to be safe and efficacious in PAH associated with the scleroderma spectrum of disease and has now been utilized in PAH associated with congenital heart disease, HIV, portal hypertension, drugs and toxin and connective tissue diseases. Epoprostenol has also been used in children of all ages with similar safety and efficacy as shown in adult patients. DISCUSSION: Due to the mode of delivery of epoprostenol, i.e. continuous intravenous infusion 24/7 via an indwelling central venous line, there are significant side effects than can occur with its use, e.g. bacteremia, sepsis, thromboembolic events, that can be fatal. Furthermore, there is significant variability in the optimal dose in both children and adult patients. It remains unclear why there is such dose variability between patients to achieve optimal efficacy. Furthermore, its mechanism(s) of action remain unclear.

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