Wang Chen, Jing Zhi-Cheng, Huang Yi-Gao, Zhou Da-Xin, Liu Zhi-Hong, Meier Christian, Nikkho Sylvia, Curram John, Zhang Peng, He Jian-Guo
Department of Respiratory Medicine , Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders , Beijing , China.
State Key Laboratory of Cardiovascular Disease , Fuwai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences , Beijing , China.
Heart Asia. 2016 May 17;8(1):74-82. doi: 10.1136/heartasia-2015-010712. eCollection 2016.
PATENT-1 and CHEST-1 were pivotal, international phase III trials assessing riociguat for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Here we compare Chinese patients from these studies with the overall populations, and report the clinical effect and safety of riociguat in Chinese patients with PAH and CTEPH.
PATENT-1 was a 12-week, randomised, double-blind, placebo-controlled trial of riociguat (maximum 2.5 mg three times daily or 1.5 mg three times daily (exploratory) in patients with PAH. CHEST-1 was a 16-week, randomised, double-blind, placebo-controlled trial of riociguat (maximum 2.5 mg three times daily) in patients with inoperable CTEPH or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy. The primary endpoint in each study was change from baseline to study end in 6 min walking distance (6MWD). Secondary endpoints included pulmonary vascular resistance (PVR), N-terminal prohormone of brain natriuretic peptide, WHO functional class (FC), and time to clinical worsening.
Chinese patients in PATENT-1 (n=77) and CHEST-1 (n=32) were younger and had better baseline 6MWD and WHO FC versus the overall population. Riociguat increased 6MWD versus placebo in Chinese patients in PATENT-1 and CHEST-1, with a greater increase observed in CHEST-1 (least-squares mean differences +46 m and +102 m in PATENT-1 and CHEST-1, respectively). Riociguat also improved several secondary endpoints in both studies, and was well tolerated.
Chinese patients displayed differences in baseline characteristics versus the overall populations in PATENT-1 and CHEST-1. Riociguat improved 6MWD, PVR, WHO FC, and other clinical outcomes in Chinese patients with PAH or CTEPH.
PATENT-1: NCT00810693, Results; CHEST-1 NCT00855465, Results.
PATENT-1和CHEST-1是评估利奥西呱用于治疗肺动脉高压（PAH）和慢性血栓栓塞性肺动脉高压（CTEPH）的关键国际III期试验。在此，我们将这些研究中的中国患者与总体人群进行比较，并报告利奥西呱在中国PAH和CTEPH患者中的临床疗效和安全性。
PATENT-1是一项为期12周的随机、双盲、安慰剂对照试验，研究利奥西呱（最大剂量为每日三次，每次2.5 mg或每日三次，每次1.5 mg（探索性））用于PAH患者。CHEST-1是一项为期16周的随机、双盲、安慰剂对照试验，研究利奥西呱（最大剂量为每日三次，每次2.5 mg）用于无法手术的CTEPH患者或肺动脉内膜剥脱术后持续/复发肺动脉高压患者。每项研究的主要终点是从基线到研究结束时6分钟步行距离（6MWD）的变化。次要终点包括肺血管阻力（PVR）、脑钠肽前体N末端、世界卫生组织功能分级（FC）以及临床恶化时间。
PATENT-1（n = 77）和CHEST-1（n = 32）中的中国患者比总体人群更年轻，基线6MWD和世界卫生组织FC更好。在PATENT-1和CHEST-1中，与安慰剂相比，利奥西呱使中国患者的6MWD增加，CHEST-1中增加幅度更大（PATENT-1和CHEST-1中最小二乘均值差异分别为+46 m和+102 m）。在两项研究中，利奥西呱还改善了几个次要终点，且耐受性良好。
PATENT-1和CHEST-1中的中国患者与总体人群在基线特征上存在差异。利奥西呱改善了中国PAH或CTEPH患者的6MWD、PVR、世界卫生组织FC及其他临床结局。
PATENT-1：NCT00810693，结果；CHEST-1：NCT00855465，结果。
