Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter?
Open Access
- 17 June 2008
- journal article
- review article
- Published by Oxford University Press (OUP) in European Heart Journal
- Vol. 29 (16), 1936-1948
- https://doi.org/10.1093/eurheartj/ehn234
Abstract
Treatment options for pulmonary arterial hypertension (PAH) have considerably improved in the past few years. Endothelin (ET)-receptor antagonism has been established as a first-line option for the majority of PAH patients. Endothelin-receptor antagonists (ETRAs) comprise sulfonamide and non-sulfonamide agents with different affinities for ET-receptor subtypes (ETA and ETB), and the focus of development has shifted from drugs with less selectivity to those with high selectivity. There is ongoing debate as to whether selective or non-selective ET-receptor antagonism is more beneficial in the treatment of PAH. This paper reviews the current evidence from experimental and clinical studies obtained from a thorough literature search focusing on the three marketed drugs bosentan, sitaxentan, and ambrisentan. A clinically meaningful difference among the three approved ETRAs with respect to their ET-receptor selectivity could not be demonstrated to date. Therefore, in clinical practice, other features are likely to be of greater relevance when considering treatment, such as the potential for serious drug–drug interactions, convenience of dosing schedule, or rates of limiting side effects. These characteristics bear more relation to the chemical or pharmacological properties of the drugs than to receptor selectivity itself.Keywords
This publication has 98 references indexed in Scilit:
- Selective endothelinA receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue diseaseAnnals Of The Rheumatic Diseases, 2007
- Results of European post-marketing surveillance of bosentan in pulmonary hypertensionEuropean Respiratory Journal, 2007
- Effects of bosentan, an endothelin receptor antagonist, on bile salt export pump and multidrug resistance–associated protein 2Biopharmaceutics & Drug Disposition, 2006
- Bosentan treatment for pulmonary arterial hypertension related to connective tissue disease: a subgroup analysis of the pivotal clinical trials and their open-label extensionsAnnals Of The Rheumatic Diseases, 2006
- Elevated Placental Growth Factor Levels Are Associated With Adverse Outcomes at Four-Year Follow-Up in Patients With Acute Coronary SyndromesJournal of the American College of Cardiology, 2006
- Treatment of Pulmonary Arterial HypertensionNew England Journal of Medicine, 2004
- Endothelin-1 stimulates human colonic myofibroblast contraction and migrationGut, 2002
- Endothelin-1 induces an increase in total protein synthesis and expression of the smooth muscle α-actin gene in vascular smooth muscle cellsLife Sciences, 1996
- Endothelin Adrenocortical Secretagogue Effect Is Mediated by the B Receptor in RatsHypertension, 1996
- Endothelin, an endothelial‐dependent vasoconstrictor in scleroderma. Enhanced production and profibrotic actionArthritis & Rheumatism, 1991