title: Evaluation of efficacy, safety and tolerability of Ambrisentan in Chinese adults with pulmonary arterial hypertension: a prospective open label cohort study.
abstract: Although several new drugs have been approved in recent years, pulmonary arterial hypertension (PAH) remains a rapidly progressive disease with a poor prognosis. Ambrisentan, a selective endothelin type A antagonist, has been approved for treatment of PAH. This open label study assessed the efficacy and safety of ambrisentan in Chinese subjects with PAH.
  
  
  
  Eligible patients with PAH (World Health Organisation [WHO] functional class [FC] II orIII) were enrolled and received Ambrisentan (5 mg) once daily for a 12-week preliminary evaluation period, and a 12-week dose-adjustment period (dose titration to 10 mgallowed). Endpoints included: change from baseline in 6-Minute Walk Distance (6-MWD), N-Terminal Pro B-Type Natriuretic Peptide (NT-pro-BNP), WHO FC, Borg Dyspnoea Index (BDI), clinical worsening of PAH and incidences of adverse events (AE).
  
  
  
  One hundred thirty-three subjects (85 % women, mean age: 36 years) with PAH (WHOFC II or III) were enrolled and received ambrisentan (5 mg) once daily for a 12-week preliminary evaluation period, and a 12-week dose-adjustment period. Mean (SD) duration of drug exposure was 161.7 (27.13) days. Ambrisentan (average daily dose of 6.27 mg) significantly improved exercise capacity (6MWD) from baseline (mean: 377.1 m [m]) at week 12 (+53.6 m, p < 0.001) (primary endpoint). Improvement in exercise capacity was noted as early as week 4, and was sustained up to week 24 (+ 64.4 m, p < 0.001). NT-pro-BNP plasma levels decreased significantly (p < 0.001) at week 12 (-861.4 ng/L) and week 24 (-806 ng/L) from baseline (mean: 1600.7 ng/L). The WHO FC showed improvements for 44 subjects at week 12 and 51 subjects at week 24. BDI scores decreased significantly at week 12 (-0.3, p < 0.001) and week 24 (-0.2, p = 0.003) from baseline (mean: 2.5). Four patients died during the study (sudden cardiac death [n = 2], cerebral haemorrhage [n = 1], cardiac failure [n = 1]). Drug related adverse events occurred in 34.3 % of subjects; peripheral oedema (11.2 %) and flushing (8.2 %) occurred most frequently.
  
  
  
  Ambrisentan (5 and 10 mg, orally) significantly improved the exercise capacity in Chinese PAH subjects with a safety profile similar to that observed in global studies.
  
  
  
  NCT No. (ClinicalTrials.gov): NCT01808313 ; Registration date (first time): February 28, 2013.
authors: Cardiovascular, 1st Affiliated Hospital of Peking University, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, China. huoyong@263.net.cn.
authors: Y
authors: Y
authors: Huo
authors: State Key Laboratory of Cardiovascular Disease, FuWai Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors: Z C
authors: ZC
authors: Jing
authors: Rheumatology and Immunology, Peking Union Medical College Hospital, Beijing, China.
authors: X F
authors: XF
authors: Zeng
authors: Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji Univeristy, Shanghai, China.
authors: J M
authors: JM
authors: Liu
authors: Cardiovascular, Xiangya Hospital Central-South University, Hunan, China.
authors: Z X
authors: ZX
authors: Yu
authors: Cardiovascular, Wuhan Asia Heart Hospital, Hubei, China.
authors: G C
authors: GC
authors: Zhang
authors: Rheumatology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Y
authors: Y
authors: Li
authors: Cardiovascular, Beijing Shijitan Hospital, Beijing, China.
authors: Y
authors: Y
authors: Wang
authors: Ministry of Public Health & Department of Cardiology, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Qilu Hospital, Shandong University, Shandong, China.
authors: Q S
authors: QS
authors: Ji
authors: Department of Clinical Immunology, 1st Affiliated Hospital of the Forth Military Medical University, Shaanxi, China.
authors: P
authors: P
authors: Zhu
authors: Cardiovascular, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: B X
authors: BX
authors: Wu
authors: Cardiovascular, 1st Hospital of Jilin University, Changchun, China.
authors: Y
authors: Y
authors: Zheng
authors: GlaxoSmithKline, Pudong, Shanghai, China.
authors: P P
authors: PP
authors: Wang
authors: GlaxoSmithKline, Pudong, Shanghai, China.
authors: J
authors: J
authors: Li
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage; D002681:China / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009017:Morbidity / Q000639:trends; D010666:Phenylpropionates / Q000008:administration & dosage*; D011446:Prospective Studies; D011724:Pyridazines / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D010666:Phenylpropionates; D011724:Pyridazines; C467894:ambrisentan
keywords: Ambrisentan; Chinese; Exercise capacity; Pulmonary arterial hypertension