Ambrisentan for the treatment of adults with pulmonary arterial hypertension: a review

Curr Med Res Opin. 2015;31(9):1793-807. doi: 10.1185/03007995.2015.1074890. Epub 2015 Aug 27.


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).

Research design and 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 ( 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.

Keywords: Ambrisentan; Clinical trials; Post-marketing product surveillance; Pulmonary arterial hypertension.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Endothelin A Receptor Antagonists / pharmacology
  • Exercise Tolerance / drug effects
  • Humans
  • Hypertension, Pulmonary* / drug therapy
  • Hypertension, Pulmonary* / physiopathology
  • Pharmacovigilance
  • Phenylpropionates / pharmacology*
  • Pyridazines / pharmacology*
  • Tadalafil / pharmacology*
  • Treatment Outcome
  • Vasodilator Agents / pharmacology


  • Endothelin A Receptor Antagonists
  • Phenylpropionates
  • Pyridazines
  • Vasodilator Agents
  • Tadalafil
  • ambrisentan

Associated data