title: Darusentan, a selective endothelin A receptor antagonist, for the oral treatment of resistant hypertension.
abstract: Resistant hypertension is defined as failure to lower blood pressure to target when a patient adheres to the maximum tolerated doses of three antihypertensive drugs including a diuretic. Notwithstanding the wide availability of several antihypertensive agents and the continued recommendation of dietary and lifestyle modifications, the prevalence of resistant hypertension remains high and is expected to increase thus underscoring the need for potential new treatment modalities in resistant hypertension. Endothelin-1 is a long-lasting potent vasoconstrictor and plays a key role in cardiovascular haemostasis. Endothelin mediates its biological activity in humans through the endothelin A and B receptors. The clinical experience and the evidence for therapy with darusentan in resistant systemic hypertension are reviewed. The leading journals that publish basic science and clinical research in the area of cardiovascular diseases and PubMed were scanned. While results from early clinical studies suggested that darusentan might emerge as new treatment option in patients with resistant hypertension, results from recent studies suggests that darusentan appears unlikely to find its way in the armamentarium for treatment of resistant hypertension.
authors.affiliation: Cardiovascular Center Cardiology, University Hospital, Rämistrasse 100, 8091 Zürich, Switzerland. frank.enseleit@usz.ch
authors.forename: Frank
authors.initials: F
authors.lastname: Enseleit
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: Frank
authors.initials: F
authors.lastname: Ruschitzka
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects*; D004351:Drug Resistance; D065130:Endothelin A Receptor Antagonists; D019317:Evidence-Based Medicine; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010666:Phenylpropionates / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D044022:Receptor, Endothelin A / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D010666:Phenylpropionates; D011743:Pyrimidines; D044022:Receptor, Endothelin A; C107831:darusentan