Long-Term Ambrisentan Therapy for the Treatment of Pulmonary Arterial Hypertension

Ronald J. Oudiz, Nazzareno Galiè, Horst Olschewski, Fernando Torres, Adaani Frost, Hossein A. Ghofrani, David B. Badesch, Michael D. McGoon, Vallerie V. McLaughlin, Ellen B. Roecker, Brooke C. Harrison, Darrin Despain, Christopher Dufton, Lewis J. Rubin

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Abstract

Objectives: This study evaluated the safety and efficacy of ambrisentan for a period of 2 years in patients with pulmonary arterial hypertension (PAH). Background: Ambrisentan is an oral, once-daily endothelin receptor antagonist that is selective for the endothelin type A receptor. The ARIES-1 (Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Studies) and ARIES-2 trials were the pivotal 12-week, placebo-controlled studies that led to the regulatory approval of ambrisentan (5 and 10 mg) for the treatment of PAH. Methods: In the ARIES-1 and -2 studies, and the subsequent long-term extension protocol, the ARIES-E study, 383 patients received ambrisentan (2.5, 5, or 10 mg). Efficacy and safety assessments are presented from the time of the first dose of ambrisentan for all patients with post-baseline data. Results: After 2 years of ambrisentan exposure, the mean change from baseline in 6-min walk distance was improved for the 5-mg (+23 m; 95% confidence interval: 9 to 38 m) and 10-mg (+28 m; 95% confidence interval: 11 to 45 m) groups. Estimates of survival and freedom from clinical worsening for the combined dose group were 94% and 83%, respectively, at 1 year and 88% and 72%, respectively, at 2 years. The annualized risk of aminotransferase abnormalities >3× the upper limit of normal was ∼2% per year; most of these events were mild and did not lead to discontinuation of drug. Conclusions: Two years of ambrisentan treatment was associated with sustained improvements in exercise capacity and a low risk of clinical worsening and death in patients with PAH. Ambrisentan was generally well tolerated and had a low risk of aminotransferase abnormalities over the 2-year study period. (A Long Term Study of Ambrisentan in Pulmonary Arterial Hypertension Subjects Having Completed AMB-320 or AMB-321; NCT00578786).

Original languageEnglish (US)
Pages (from-to)1971-1981
Number of pages11
JournalJournal of the American College of Cardiology
Volume54
Issue number21
DOIs
StatePublished - Nov 17 2009

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Keywords

  • ambrisentan
  • endothelin
  • exercise capacity
  • hypertension
  • long-term survival
  • pulmonary

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Oudiz, R. J., Galiè, N., Olschewski, H., Torres, F., Frost, A., Ghofrani, H. A., Badesch, D. B., McGoon, M. D., McLaughlin, V. V., Roecker, E. B., Harrison, B. C., Despain, D., Dufton, C., & Rubin, L. J. (2009). Long-Term Ambrisentan Therapy for the Treatment of Pulmonary Arterial Hypertension. Journal of the American College of Cardiology, 54(21), 1971-1981. https://doi.org/10.1016/j.jacc.2009.07.033