Journalartikel

Jahr der Veröffentlichung: 2009

Seiten: 1971-1981

Zeitschrift: Journal of the American College of Cardiology

Bandnummer: 54

Heftnummer: 21

ISSN: 0735-1097

eISSN: 1558-3597

DOI Link: https://doi.org/10.1016/j.jacc.2009.07.033

Verlag: Elsevier

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 >3x the upper limit of normal was similar to 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) (J Am Coll Cardiol 2009; 54: 1971-81) (C) 2009 by the American College of Cardiology Foundation

Harvard-Zitierstil: Oudiz, R., Galie, N., Olschewski, H., Torres, F., Frost, A., Ghofrani, H., et al. (2009) Long-Term Ambrisentan Therapy for the Treatment of Pulmonary Arterial Hypertension, Journal of the American College of Cardiology, 54(21), pp. 1971-1981. https://doi.org/10.1016/j.jacc.2009.07.033

APA-Zitierstil: Oudiz, R., Galie, N., Olschewski, H., Torres, F., Frost, A., Ghofrani, H., Badesch, D., McGoon, M., McLaughlin, V., Roecker, E., Harrison, B., Despain, D., Dufton, C., & Rubin, L. (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