title: Developments in pulmonary arterial hypertension-targeted therapy for chronic thromboembolic pulmonary hypertension.
abstract: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease characterised by the presence of organised chronic thromboembolic material occluding the proximal pulmonary arteries and a vasculopathy in the distal pulmonary arterial tree. Pulmonary endarterectomy (PEA) is a potential cure for many patients with CTEPH. However, PEA is not suitable for patients with a significant distal distribution of chronic thromboembolic material or with significant comorbidities. Also, a proportion of patients are left with residual CTEPH post PEA. Until recently, pulmonary arterial hypertension-targeted therapies have been used off licence to treat patients with inoperable or residual CTEPH. The CHEST1 study investigated the use of riociguat and was the first randomised controlled trial to show efficacy in inoperable or residual CTEPH. In this review, we explore the pathophysiology of CTEPH and review the current trial evidence for pulmonary arterial hypertension-targeted therapies. We also include a discussion of physiological considerations that require further investigation.
authors.affiliation: a Pulmonary Vascular Diseases Unit, Papworth Hospital, Papworth Everard, Cambridge, CB23 3RE, UK.
authors.forename: Charaka
authors.initials: C
authors.lastname: Hadinnapola
authors.forename: Joanna
authors.initials: J
authors.lastname: Pepke-Zaba
mesh_terms: D002908:Chronic Disease; D065128:Endothelin Receptor Antagonists / Q000627:therapeutic use; D006162:Guanylate Cyclase; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D058990:Molecular Targeted Therapy; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use; D011453:Prostaglandins / Q000627:therapeutic use; D011655:Pulmonary Embolism / Q000150:complications*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D000071756:Soluble Guanylyl Cyclase
chemical_list: D065128:Endothelin Receptor Antagonists; D058986:Phosphodiesterase 5 Inhibitors; D011453:Prostaglandins; D018160:Receptors, Cytoplasmic and Nuclear; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase
keywords: chronic thromboembolic pulmonary hypertension; clinical trials; pathophysiology; pulmonary arterial hypertension; pulmonary arterial hypertension–targeted therapy; riociguat