title: Optimizing endothelin receptor antagonist use in the management of pulmonary arterial hypertension.
abstract: Endothelin receptor antagonism has emerged as an important therapeutic approach in pulmonary arterial hypertension (PAH). Bench to bedside scientific research has shown that endothelin-1 (ET-1) is overexpressed in several forms of pulmonary vascular disease and may play an important pathogenetic role in the development and progression of PAH. Oral endothelin receptor antagonists (ERAs) improved exercise capacity, functional status, pulmonary hemodynamics, and delayed the time to clinical worsening in several randomized placebo-controlled trials. Two ERAs are currently approved by the US Food and Drug Administration: bosentan, a dual ERA for patients with class III and IV PAH, and ambrisentan, a selective ERA for patients with class II and III PAH. Sitaxsentan, another selective ERA, has been approved in Europe, Canada, and Australia. The objective of this review is to evaluate the available evidence describing the pharmacology, efficacy, safety, and tolerability, and patient-focused perspectives regarding the different types of endothelin receptor antagonists. Ongoing and forthcoming randomized trials are also highlighted including the approach of combining this class of drugs with other drugs that target different cellular pathways believed to be etiologically important in PAH.
authors.affiliation: Pulmonary Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: M Kathryn
authors.initials: MK
authors.lastname: Steiner
authors.forename: Ioana R
authors.initials: IR
authors.lastname: Preston
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077300:Bosentan; D004359:Drug Therapy, Combination; D065128:Endothelin Receptor Antagonists; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000378:metabolism; D007555:Isoxazoles / Q000627:therapeutic use; D010349:Patient Compliance; D017060:Patient Satisfaction; D010666:Phenylpropionates / Q000627:therapeutic use; D011724:Pyridazines / Q000627:therapeutic use; D011788:Quality of Life; D017466:Receptors, Endothelin / Q000378:metabolism; D013449:Sulfonamides / Q000627:therapeutic use; D013876:Thiophenes / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D007555:Isoxazoles; D010666:Phenylpropionates; D011724:Pyridazines; D017466:Receptors, Endothelin; D013449:Sulfonamides; D013876:Thiophenes; C467894:ambrisentan; C106276:sitaxsentan; D000077300:Bosentan