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

被引：193

作者：

Oudiz, Ronald J. ^{[1
]}

Galie, Nazzareno ^{[2
]}

Olschewski, Horst ^{[3
]}

Torres, Fernando ^{[4
]}

Frost, Adaani ^{[5
]}

Ghofrani, Hossein A. ^{[6
]}

Badesch, David B. ^{[7
]}

McGoon, Michael D. ^{[8
]}

McLaughlin, Vallerie V. ^{[9
]}

Roecker, Ellen B. ^{[10
]}

Harrison, Brooke C. ^{[11
]}

Despain, Darrin ^{[11
]}

Dufton, Christopher ^{[11
]}

Rubin, Lewis J. ^{[12
]}

机构：

[1] Harbor UCLA Med Ctr, Dept Med, Div Cardiol, LA Biomed Res Inst Harbor UCLA, Torrance, CA 90502 USA

[2] Univ Bologna, Cardiol Inst, Bologna, Italy

[3] Med Univ Graz, Graz, Austria

[4] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA

[5] Baylor Coll Med, Houston, TX 77030 USA

[6] Univ Giessen, Lung Ctr, Giessen, Germany

[7] Univ Colorado, Denver, CO 80202 USA

[8] Mayo Clin, Rochester, MN USA

[9] Univ Michigan, Ann Arbor, MI 48109 USA

[10] Univ Wisconsin, Madison, WI USA

[11] Gilead Sci Inc, Boulder, CO USA

[12] UCSD, La Jolla, CA USA

来源：

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY | 2009年 / 54卷 / 21期

关键词：

ambrisentan; exercise capacity; endothelin; hypertension; pulmonary; long-term survival; NITRIC-OXIDE; 1ST-LINE BOSENTAN; SURVIVAL; ENDOTHELIN-1; SITAXSENTAN; 1-YEAR;

D O I：

10.1016/j.jacc.2009.07.033

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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

引用

页码：1971 / 1981

页数：11

共 29 条

[1] Long-term outcome in pulmonary arterial hypertension patients treated with subcutaneous treprostinil [J].