ARIES-3: ambrisentan therapy in a diverse population of patients with pulmonary hypertension

Cardiovasc Ther. 2012 Apr;30(2):93-9. doi: 10.1111/j.1755-5922.2011.00279.x. Epub 2011 Jun 20.


Introduction: Ambrisentan is an oral, once daily, endothelin receptor antagonist approved for treatment of pulmonary arterial hypertension (PAH). Previous studies of ambrisentan were limited to patients with Group 1 PAH and often excluded patients receiving other pulmonary hypertension (PH) therapies.

Aims: ARIES-3 was an open-label study evaluating efficacy and safety of ambrisentan in patients with various PH etiologies and background PH medications. Patients received 5 mg ambrisentan once daily for 24 weeks. The primary endpoint was change from baseline in 6-minute walk distance (6MWD) at week 24.

Results: A total of 224 patients with PH due to idiopathic and familial PAH (31%), connective tissue disease (18%), chronic hypoxemia (22%), chronic thromboembolic disease (13%), or other etiologies (16%) were enrolled and 53% of patients received stable background PAH therapies. After 24 weeks of therapy, an increase in 6MWD (+21 m; 95% CI: 12-29) and a decrease in B-type natriuretic peptide (-26%; 95% CI: -34 to -16%) was observed in the overall population compared to baseline; however, increases in 6MWD were not observed in several non-Group 1 PH subpopulations. Peripheral edema, headache, and dyspnea were the most common adverse events.

Conclusion: This study reconfirms the results of previous placebo-controlled studies, which demonstrate that ambrisentan is well tolerated and provides benefit in patients with PAH. Definitive conclusions regarding the safety and efficacy of ambrisentan in specific non-Group 1 PH etiologies cannot be determined and larger, controlled studies will be necessary to determine the efficacy and safety of ambrisentan in these populations.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Double-Blind Method
  • Endothelin A Receptor Antagonists
  • Exercise Tolerance
  • Female
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Long-Term Care
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain
  • Phenylpropionates / adverse effects
  • Phenylpropionates / therapeutic use*
  • Pyridazines / adverse effects
  • Pyridazines / therapeutic use*
  • Survival
  • Treatment Outcome
  • Walking / physiology


  • Endothelin A Receptor Antagonists
  • Phenylpropionates
  • Pyridazines
  • Natriuretic Peptide, Brain
  • ambrisentan