Evaluation of efficacy, safety and tolerability of Ambrisentan in Chinese adults with pulmonary arterial hypertension: a prospective open label cohort study

BMC Cardiovascular Disorders

Research Article

Y. Huo¹  Y. Zheng²  Y. Wang³  B. X. Wu⁴  G. C. Zhang⁵  Z. X. Yu⁶  P. Zhu⁷  J. Li⁸  P. P. Wang⁸  Q. S. Ji⁹  J. M. Liu^1,10  X. F. Zeng^1,11  Y. Li^1,12  Z. C. Jing^1,13 

[1] Cardiovascular, 1st Affiliated Hospital of Peking University, No. 8 Xishiku Street, 100034, Beijing, Xicheng District, China;Cardiovascular, 1st Hospital of Jilin University, Changchun, China;Cardiovascular, Beijing Shijitan Hospital, Beijing, China;Cardiovascular, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China;Cardiovascular, Wuhan Asia Heart Hospital, Hubei, China;Cardiovascular, Xiangya Hospital Central-South University, Hunan, China;Department of Clinical Immunology, 1st Affiliated Hospital of the Forth Military Medical University, Shaanxi, China;GlaxoSmithKline, Shanghai, Pudong, China;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;Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji Univeristy, Shanghai, China;Rheumatology and Immunology, Peking Union Medical College Hospital, Beijing, China;Rheumatology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China;State Key Laboratory of Cardiovascular Disease, FuWai Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China;

关键词: Ambrisentan;    Chinese;    Exercise capacity;    Pulmonary arterial hypertension;   

DOI  :  10.1186/s12872-016-0361-9

 received in 2016-01-16, accepted in 2016-09-27,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundAlthough 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.MethodsEligible 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).ResultsOne 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.ConclusionAmbrisentan (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.Trial registrationNCT No. (ClinicalTrials.gov): NCT01808313; Registration date (first time): February 28, 2013.

【 授权许可】

CC BY   
© The Author(s). 2016