The prostacyclin pathway in pulmonary arterial hypertension: a clinical review

ABSTRACT

Introduction: 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.

KEYWORDS:

• Beraprost
• epoprostenol
• iloprost
• prostacyclin
• prostanoids
• pulmonary arterial hypertension
• selexipag
• treprostinil

Acknowledgments

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Medical writing assistance was provided by Content Ed Net (Madrid, Spain), with funding from Actelion Pharmaceuticals. Actelion did not have any role in the collection, analysis, and interpretation of data or writing the report. The views expressed are therefore based on author’s opinions and do not represent the views of Actelion or the journal.

Additional information

Funding

This paper was funded by Actelion Pharmaceuticals.