title: The prostacyclin pathway in pulmonary arterial hypertension: a clinical review.
abstract: Prostacyclin is produced in vascular endothelial cells and acts via the IP prostacyclin receptor to cause vasodilation and inhibit smooth muscle cell proliferation and platelet aggregation. Prostacyclin production is reduced in pulmonary arterial hypertension (PAH), and drugs targeting the prostacyclin pathway are one of the pharmacotherapeutic options for PAH. Areas covered: The prostacyclin pathway and drugs that target it are discussed, including synthetic prostacyclin (epoprostenol), prostacyclin analogs (iloprost, treprostinil, beraprost) and selective prostacyclin IP receptor agonists (selexipag). An overview of the development of these therapies, from the earlier agents requiring parenteral administration, through inhaled formulations, to oral products, is provided, together with a summary of data from key clinical trials and registries. Expert commentary: Synthetic prostacyclin and prostacyclin analogs are beneficial for patients with PAH, but they tend to be underused, in part due to the difficulties associated with the administration of parenteral and inhaled formulations. Oral prostacyclin analogs have some limitations with regard to efficacy. The newest agent targeting the prostacyclin pathway, the selective prostacyclin receptor agonist selexipag, is administered orally, and has been shown to reduce a composite morbidity/mortality endpoint. Ongoing studies will help clarify how best to use it in the management of PAH.
authors.affiliation: a Pulmonary Hypertension Unit, Pneumonology Department , Hospital Universitario 12 de Octubre, Madrid , Spain.
authors.forename: R
authors.initials: R
authors.lastname: Del Pozo
authors.affiliation: b Pulmonary Hypertension Unit, Cardiology Department , Hospital Universitario 12 de Octubre, Madrid , Spain .
authors.forename: I
authors.initials: I
authors.lastname: Hernandez Gonzalez
authors.affiliation: b Pulmonary Hypertension Unit, Cardiology Department , Hospital Universitario 12 de Octubre, Madrid , Spain .
authors.forename: P
authors.initials: P
authors.lastname: Escribano-Subias
mesh_terms: D000081:Acetamides / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000378:metabolism*; D011719:Pyrazines / Q000627:therapeutic use; D044006:Receptors, Epoprostenol / Q000378:metabolism*
chemical_list: D000081:Acetamides; D000959:Antihypertensive Agents; D011719:Pyrazines; D044006:Receptors, Epoprostenol; C048081:beraprost; C523468:selexipag; D011464:Epoprostenol; C427248:treprostinil
keywords: Beraprost; epoprostenol; iloprost; prostacyclin; prostanoids; pulmonary arterial hypertension; selexipag; treprostinil