Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: a long-term extension study (CHEST-2).
Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of inoperable and persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). In the 16-week CHEST-1 study, riociguat showed a favourable benefit-risk profile and improved several clinically relevant end-points in patients with CTEPH. The CHEST-2 open-label extension evaluated the long-term safety and efficacy of riociguat. Eligible patients from CHEST-1 received riociguat individually adjusted up to a maximum dose of 2.5 mg three times daily. The primary objective was the safety and tolerability of riociguat; exploratory efficacy end-points included 6-min walking distance (6MWD) and World Health Organization (WHO) functional class (FC). Overall, 237 patients entered CHEST-2 and 211 (89%) were ongoing at this interim analysis (March 2013). The safety profile of riociguat in CHEST-2 was similar to CHEST-1, with no new safety signals. Improvements in 6MWD and WHO FC observed in CHEST-1 persisted for up to 1 year in CHEST-2. In the observed population at 1 year, mean±sd 6MWD had changed by +51±62 m (n=172) versus CHEST-1 baseline (n=237), and WHO FC had improved/stabilised/worsened in 47/50/3% of patients (n=176) versus CHEST-1 baseline (n=236). Long-term riociguat had a favourable benefit-risk profile and apparently showed sustained benefits in exercise and functional capacity for up to 1 year.
Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Bicêtre, Université Paris-Sud, Laboratoire d'Excellence en Recherche sur le Médicament et Innovation Thérapeutique, and INSERM Unité 999, Le Kremlin-Bicêtre, France gerald.simonneau@abc.ap-hop-paris.fr.
Gérald
G
Simonneau
Division of Cardiothoracic Surgery, Foundation "I.R.C.C.S. Policlinico San Matteo", University of Pavia School of Medicine, Pavia, Italy.
Andrea M
AM
D'Armini
University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany, and Member of the German Center of Lung Research (DZL) Dept of Medicine, Imperial College London, London, UK.
Hossein-Ardeschir
HA
Ghofrani
University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany, and Member of the German Center of Lung Research (DZL).
Friedrich
F
Grimminger
Clinic for Respiratory Medicine, Hannover Medical School, Hannover, Germany, and Member of the German Center of Lung Research (DZL).
Marius M
MM
Hoeper
Clinical Dept of Cardiology and Angiology, First Faculty of Medicine and General Teaching Hospital, Prague, Czech Republic.
Pavel
P
Jansa
Division of Pulmonary and Critical Care Medicine, School of Medicine, University of California San Diego, San Diego, CA, USA.
Nick H
NH
Kim
Beijing Institute of Respiratory Medicine, Beijing Chao Yang Hospital, Dept of Respiratory Medicine, Capital Medical University, Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Beijing, China.
Chen
C
Wang
National Institute for Health Research/Wellcome Trust Imperial Clinical Research Facility, Imperial Centre for Translational and Experimental Medicine, Imperial College London, London, UK.
Martin R
MR
Wilkins
Global Clinical Development, Bayer HealthCare Pharmaceuticals, Wuppertal, Germany.
Arno
A
Fritsch
Global Clinical Development, Bayer HealthCare Pharmaceuticals, Wuppertal, Germany.
Neil
N
Davie
Global Clinical Development, Bayer HealthCare Pharmaceuticals, Barcelona, Spain.
Pablo
P
Colorado
Kerckhoff Heart and Lung Center, Bad Nauheim, Germany.
Eckhard
E
Mayer
D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012129:Respiratory Function Tests; D012306:Risk; D013923:Thromboembolism / Q000188:drug therapy*; D013997:Time Factors; D016138:Walking
D000959:Antihypertensive Agents; D011720:Pyrazoles; D011743:Pyrimidines; D006162:Guanylate Cyclase; C542595:riociguat