title: Ambrisentan for the treatment of adults with pulmonary arterial hypertension: a review.
abstract: OBJECTIVE
  To provide an overview of the drug profile of the orally active, selective endothelin A receptor antagonist ambrisentan, and its efficacy and safety in the treatment of patients with pulmonary arterial hypertension (PAH).
  
  
  METHODS
  Medical literature on the use of ambrisentan in PAH was identified using MEDLINE and EMBASE. Additional references were identified from the reference lists of published articles and from the authors' own bibliographies.
  
  
  RESULTS
  Significant improvements in exercise capacity were observed with approved dosages of ambrisentan (5 or 10 mg once daily) in the AMB-220 dose-ranging study and the pivotal ARIES-1 and ARIES-2 trials, with sustained effects up to 2 years observed in ARIES-E. Improvements in cardiopulmonary hemodynamic variables were reported in AMB-220 and ARIES-E (subset analysis). Ambrisentan had little or no effect on hepatic transporters in in vitro studies and displayed a low risk of potential drug-drug interactions, including those with other PAH therapies. Results from the VOLT post-marketing program confirmed the safety profile of ambrisentan observed in the ARIES studies, including the low incidence of liver function test abnormalities. Peripheral edema and anemia were common side effects of endothelin receptor antagonist therapies, including ambrisentan. In the recently completed AMBITION study (ClinicalTrials.gov Identifier: NCT01178073), upfront initial combination therapy with ambrisentan and tadalafil significantly reduced the risk of clinical failure (primary endpoint) by 50% compared with the pooled monotherapy groups.
  
  
  CONCLUSIONS
  The long-term efficacy and safety profile of ambrisentan in patients with PAH is supported by data from a comprehensive clinical trial program and real-life, post-marketing observations.
authors.affiliation: a a Scottish Pulmonary Vascular Unit, Regional Heart and Lung Centre , Glasgow , UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Peacock
authors.affiliation: b b European Immunology and Rare Diseases Unit, GlaxoSmithKline SpA , Verona , Italy.
authors.forename: William
authors.initials: W
authors.lastname: Zamboni
authors.affiliation: c c Pulmonary Hypertension Unit, Department of Cardiovascular and Respiratory Disease, Sapienza University of Rome , Rome , Italy.
authors.forename: Carmine Dario
authors.initials: CD
authors.lastname: Vizza
mesh_terms: D065130:Endothelin A Receptor Antagonists / Q000494:pharmacology; D017079:Exercise Tolerance / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology; D060735:Pharmacovigilance; D010666:Phenylpropionates / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D000068581:Tadalafil / Q000494:pharmacology*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D065130:Endothelin A Receptor Antagonists; D010666:Phenylpropionates; D011724:Pyridazines; D014665:Vasodilator Agents; D000068581:Tadalafil; C467894:ambrisentan
keywords: Ambrisentan; Clinical trials; Post-marketing product surveillance; Pulmonary arterial hypertension