Riociguat for the treatment of pulmonary hypertension: Chinese subgroup analyses and comparison.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.


BACKGROUND
PATENT-1: NCT00810693, Results; CHEST-1 NCT00855465, Results.
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.
Chen
C
Wang
State Key Laboratory of Cardiovascular Disease , Fuwai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences , Beijing , China.
Zhi-Cheng
ZC
Jing
Department of Cardiology , Guangdong General Hospital and Guangdong Cardiovascular Institute , Guangzhou, Guangdong , China.
Yi-Gao
YG
Huang
Department of Cardiology , Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases , Shanghai , China.
Da-Xin
DX
Zhou
State Key Laboratory of Cardiovascular Diseases , Fuwai Hospital, National Centre for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
Zhi-Hong
ZH
Liu
Global Clinical Development , Bayer Pharma AG , Berlin , Germany.
Christian
C
Meier
Global Clinical Development , Bayer Pharma AG , Berlin , Germany.
Sylvia
S
Nikkho
Global Development , Bayer plc , Newbury , UK.
John
J
Curram
Medical Affairs , Bayer Healthcare , Beijing , China.
Peng
P
Zhang
State Key Laboratory of Cardiovascular Diseases , Fuwai Hospital, National Centre for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
Jian-Guo
JG
He