Recent advances in targeting the prostacyclin pathway in pulmonary arterial hypertension

• Published in: European respiratory review Vol. 24; no. 138; pp. 630 - 641
• Main Authors: Lang, Irene M., Gaine, Sean P.
• Format: Journal Article
• Language: English
• Published: England European Respiratory Society 01.12.2015
• Subjects: Administration, Inhalation; Administration, Oral; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - adverse effects; Antihypertensive Agents - chemical synthesis; Antihypertensive Agents - therapeutic use; Arterial Pressure - drug effects; Humans; Hypertension, Pulmonary - diagnosis; Hypertension, Pulmonary - drug therapy; Hypertension, Pulmonary - metabolism; Hypertension, Pulmonary - physiopathology; Infusions, Parenteral; Molecular Targeted Therapy; Prostaglandins I - administration & dosage; Prostaglandins I - adverse effects; Prostaglandins I - chemical synthesis; Prostaglandins I - therapeutic use; Pulmonary Artery - drug effects; Pulmonary Artery - metabolism; Pulmonary Artery - physiopathology; Receptors, Epoprostenol - drug effects; Receptors, Epoprostenol - metabolism; Reviews; Severity of Illness Index; Signal Transduction - drug effects; Treatment Outcome; Vasodilator Agents - administration & dosage; Vasodilator Agents - adverse effects; Vasodilator Agents - chemical synthesis; Vasodilator Agents - therapeutic use
• ISSN: 0905-9180; 1600-0617; 1600-0617
• DOI: 10.1183/16000617.0067-2015

Pulmonary arterial hypertension (PAH) is a severe disease characterised by increased pulmonary vascular resistance, which leads to restricted pulmonary arterial blood flow and elevated pulmonary arterial pressure. In patients with PAH, pulmonary concentrations of prostacyclin, a prostanoid that targets several receptors including the IP prostacyclin receptor, are reduced. To redress this balance, epoprostenol, a synthetic prostacyclin, or analogues of prostacyclin have been given therapeutically. These therapies improve exercise capacity, functional class and haemodynamic parameters. In addition, epoprostenol improves survival among patients with PAH. Despite their therapeutic benefits, treatments that target the prostacyclin pathway are underused. One key factor is their requirement for parenteral administration: continuous intravenous administration can lead to embolism and thrombosis; subcutaneous administration is associated with infusion-site pain; and inhalation is time consuming, requiring multiple daily administrations. Nevertheless, targeting the prostacyclin pathway is an important strategy for the management of PAH. The development of oral therapies for this pathway, as well as more user-friendly delivery devices, may alleviate some of the inconveniences. Continued improvements in therapeutic options will enable more patients with PAH to receive medication targeting the prostacyclin pathway.