PMID- 32680480
OWN - NLM
STAT- MEDLINE
DCOM- 20210125
LR  - 20210125
IS  - 1471-2261 (Electronic)
IS  - 1471-2261 (Linking)
VI  - 20
IP  - 1
DP  - 2020 Jul 17
TI  - Efficacy and safety of ambrisentan in Chinese patients with connective tissue 
      disease-pulmonary arterial hypertension: a post-hoc analysis.
PG  - 339
LID - 10.1186/s12872-020-01591-1 [doi]
LID - 339
AB  - BACKGROUND: The efficacy and safety of ambrisentan has been previously evaluated 
      in Chinese patients with pulmonary arterial hypertension (PAH). This post-hoc 
      analysis assessed the efficacy and safety of ambrisentan in a subgroup of 
      connective tissue disease (CTD) patients with PAH. METHODS: In this open-label, 
      single-arm study, patients received ambrisentan 5 mg once daily for 12 weeks, 
      followed by 12-week dose titration period (dose up to 10 mg). Efficacy endpoints 
      included change from baseline in exercise capacity (measured by 6-min walk test 
      [6MWT]), N-terminal pro B type natriuretic peptide (NT-proBNP) plasma levels, WHO 
      Functional Class (FC) and Borg Dyspnoea Index (BDI) scores from baseline to weeks 
      12 and 24. Safety endpoints included time to clinical worsening and incidence of 
      adverse events (AEs). RESULTS: In total, 71 Chinese patients with CTD-PAH were 
      included in this analysis. Ambrisentan treatment significantly improved exercise 
      capacity (6MWT) from baseline (mean: 366.4 m) to week 12 (63.8 m, p < 0.001) and 
      week 24 (73.2 m, p < 0.001). A significant reduction in NT-proBNP levels was 
      observed from baseline (mean: 1837.5 ng/L) to week 12 (- 1156.8 ng/L, p < 0.001) 
      and week 24 (- 1095.5 ng/L, p < 0.001). BDI scores decreased significantly at 
      week 12 (- 0.6, p < 0.001) and week 24 (- 0.4, p = 0.002) from baseline (mean: 
      2.7). The WHO FC improved in 29 (40.8%) and 34 (47.9%) patients at weeks 12 and 
      24, respectively. Adverse events were reported in 52 (73.2%) patients. One 
      patient (1.4%) experienced clinical worsening at week 24. CONCLUSION: Ambrisentan 
      showed significant improvement in exercise capacity and no clinical worsening in 
      the majority of Chinese patients with CTD-PAH in the 24-week treatment period. 
      The AEs observed in the CTD-PAH subgroup were consistent with the known safety 
      profile of ambrisentan in the overall Chinese PAH population. TRIAL REGISTRATION: 
      ClinicalTrial.gov Identifier, https://clinicaltrials.gov/, NCT01808313 
      Registration date (first time): February 28, 2013.
FAU - Li, Mengtao
AU  - Li M
AD  - Department of Rheumatology, Peking Union Medical College Hospital, Peking Union 
      Medical College & Chinese Academy of Medical Sciences, National Clinical Research 
      Center for Immunologic Diseases, Ministry of Science & Technology, Key Laboratory 
      of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.
FAU - Jing, Zhi-Cheng
AU  - Jing ZC
AD  - Key Lab of Pulmonary Vascular Medicine & FuWai Hospital, State Key lab of 
      Cardiovascular disease, National center for Cardiovascular disease, Department of 
      Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Sciences & Peking Union Medical College, Beijing, China.
FAU - Li, Yang
AU  - Li Y
AD  - 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
FAU - Huo, Yong
AU  - Huo Y
AD  - 1st Affiliated Hospital of Peking University, Beijing, China.
FAU - Yu, Zaixin
AU  - Yu Z
AD  - Xiangya Hospital Central-South University, Changsha, Hunan, China.
FAU - Zhang, Gangcheng
AU  - Zhang G
AD  - Wuhan Asia Heart Hospital, Wuhan, Hubei, China.
FAU - Zhu, Ping
AU  - Zhu P
AD  - 1st Affiliated Hospital of the Fourth Military Medical University, Xi'an, 
      Shaanxi, China.
FAU - Liu, Jinming
AU  - Liu J
AD  - Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
FAU - Ji, Qiushang
AU  - Ji Q
AD  - Qilu Hospital, Shandong University, Jinan, Shandong, China.
FAU - Wu, Bingxiang
AU  - Wu B
AD  - 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
FAU - Zhong, Jinhua
AU  - Zhong J
AD  - GlaxoSmithKline (China) R&D Company Limited, Shanghai, China.
FAU - Wang, Pingping
AU  - Wang P
AD  - GlaxoSmithKline (China) R&D Company Limited, Shanghai, China.
FAU - Zhu, Wenjing
AU  - Zhu W
AD  - GlaxoSmithKline (China) R&D Company Limited, Shanghai, China.
FAU - Zeng, Xiaofeng
AU  - Zeng X
AUID- ORCID: 0000-0002-3883-2318
AD  - Department of Rheumatology, Peking Union Medical College Hospital, Peking Union 
      Medical College & Chinese Academy of Medical Sciences, National Clinical Research 
      Center for Immunologic Diseases, Ministry of Science & Technology, Key Laboratory 
      of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China. 
      xiaofeng.zeng@cstar.org.cn.
LA  - eng
SI  - ClinicalTrials.gov/NCT01808313
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20200717
PL  - England
TA  - BMC Cardiovasc Disord
JT  - BMC cardiovascular disorders
JID - 100968539
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Endothelin A Receptor Antagonists)
RN  - 0 (Peptide Fragments)
RN  - 0 (Phenylpropionates)
RN  - 0 (Pyridazines)
RN  - 0 (pro-brain natriuretic peptide (1-76))
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
RN  - HW6NV07QEC (ambrisentan)
SB  - IM
MH  - Adult
MH  - Antihypertensive Agents/adverse effects/*therapeutic use
MH  - Beijing
MH  - Biomarkers/blood
MH  - Connective Tissue Diseases/*complications/diagnosis
MH  - Endothelin A Receptor Antagonists/adverse effects/*therapeutic use
MH  - Exercise Tolerance/drug effects
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Natriuretic Peptide, Brain/blood
MH  - Peptide Fragments/blood
MH  - Phenylpropionates/adverse effects/*therapeutic use
MH  - Pulmonary Arterial Hypertension/diagnosis/*drug therapy/*etiology/physiopathology
MH  - Pyridazines/adverse effects/*therapeutic use
MH  - Recovery of Function
MH  - Time Factors
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC7367256
OTO - NOTNLM
OT  - Ambrisentan
OT  - Chinese
OT  - Exercise capacity
COIS- Jinhua Zhong, Wenjing Zhu and Pingping Wang were employees of GSK during the 
      conduct of this study and manuscript development. All other authors have nothing 
      to disclose.
EDAT- 2020/07/19 06:00
MHDA- 2021/01/26 06:00
PMCR- 2020/07/17
CRDT- 2020/07/19 06:00
PHST- 2019/05/29 00:00 [received]
PHST- 2020/06/16 00:00 [accepted]
PHST- 2020/07/19 06:00 [entrez]
PHST- 2020/07/19 06:00 [pubmed]
PHST- 2021/01/26 06:00 [medline]
PHST- 2020/07/17 00:00 [pmc-release]
AID - 10.1186/s12872-020-01591-1 [pii]
AID - 1591 [pii]
AID - 10.1186/s12872-020-01591-1 [doi]
PST - epublish
SO  - BMC Cardiovasc Disord. 2020 Jul 17;20(1):339. doi: 10.1186/s12872-020-01591-1.