安立生坦治疗中国结缔组织病相关性肺动脉高压患者的疗效和安全性：一项事后分析。
Efficacy and safety of ambrisentan in Chinese patients with connective tissue disease-pulmonary arterial hypertension: a post-hoc analysis.
机构信息
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.
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.
出版信息
BMC Cardiovasc Disord. 2020 Jul 17;20(1):339. doi: 10.1186/s12872-020-01591-1.
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.
背景
安贝生坦先前已在患有肺动脉高压（PAH）的中国患者中进行了疗效和安全性评估。本事后分析评估了安贝生坦在患有 PAH 的结缔组织病（CTD）患者亚组中的疗效和安全性。
方法
在这项开放标签、单臂研究中，患者接受安贝生坦 5mg 每日一次治疗 12 周，随后进行 12 周的剂量滴定期（剂量最高可达 10mg）。疗效终点包括从基线开始的运动能力（通过 6 分钟步行试验[6MWT]测量）、N 端脑利钠肽前体（NT-proBNP）血浆水平、世界卫生组织功能分级（WHO FC）和 Borg 呼吸困难指数（BDI）评分的变化，从基线到第 12 周和第 24 周。安全性终点包括临床恶化时间和不良事件（AE）的发生率。
结果
总共纳入了 71 例患有 CTD-PAH 的中国患者进行了此项分析。安贝生坦治疗可显著改善运动能力（6MWT），从基线（平均：366.4m）到第 12 周（63.8m，p<0.001）和第 24 周（73.2m，p<0.001）。从基线开始，NT-proBNP 水平显著降低（平均：1837.5ng/L），至第 12 周（-1156.8ng/L，p<0.001）和第 24 周（-1095.5ng/L，p<0.001）。第 12 周（-0.6，p<0.001）和第 24 周（-0.4，p=0.002）时，BDI 评分与基线相比显著下降（平均：2.7）。在第 12 周和第 24 周时，分别有 29 例（40.8%）和 34 例（47.9%）患者的 WHO FC 得到改善。52 例（73.2%）患者出现不良反应。1 例（1.4%）患者在第 24 周时出现临床恶化。
结论
在 24 周的治疗期间，安贝生坦显示出了在患有 CTD-PAH 的中国患者中运动能力的显著改善，且大多数患者无临床恶化。在 CTD-PAH 亚组中观察到的不良反应与安贝生坦在中国整体 PAH 人群中的已知安全性特征一致。
试验注册
ClinicalTrials.gov 标识符，https://clinicaltrials.gov/，首次注册日期（首次时间）：2013 年 2 月 28 日。
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