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Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter?Opitz CF; Ewert R; Kirch W; Pittrow DEur Heart J 2008[Aug]; 29 (16): 1936-48Treatment 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 (ET(A) and ET(B)), 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.|*Endothelin Receptor Antagonists[MESH]|Antihypertensive Agents/*therapeutic use[MESH]|Bosentan[MESH]|Endothelin-1/*antagonists & inhibitors/blood[MESH]|Female[MESH]|Humans[MESH]|Hypertension, Pulmonary/*drug therapy/mortality/physiopathology[MESH]|Isoxazoles/therapeutic use[MESH]|Male[MESH]|Phenylpropionates/therapeutic use[MESH]|Pulmonary Artery/*drug effects/physiology[MESH]|Pyridazines/therapeutic use[MESH]|Randomized Controlled Trials as Topic[MESH]|Sulfonamides/therapeutic use[MESH]|Thiophenes/therapeutic use[MESH]|Treatment Outcome[MESH]|Vascular Resistance/*drug effects[MESH]|Walking/physiology[MESH] |
