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

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

Clinic for Respiratory Medicine Hannover Medical School Hannover Germany and Member of the German Center of Lung Research

Clinical Dept of Cardiology and Angiology 1st Faculty of Medicine and General Teaching Hospital Prague Czech Republic

Division of Cardiothoracic Surgery Foundation 1 R C C S Policlinico San Matteo University of Pavia School of Medicine Pavia Italy

Division of Pulmonary and Critical Care Medicine School of Medicine University of California San Diego San Diego CA USA

Global Clinical Development Bayer HealthCare Pharmaceuticals Barcelona Spain

Global Clinical Development Bayer HealthCare Pharmaceuticals Wuppertal Germany

Kerckhoff Heart and Lung Center Bad Nauheim Germany

National Institute for Health Research Wellcome Trust Imperial Clinical Research Facility Imperial Centre for Translational and Experimental Medicine Imperial College London London UK

University of Giessen and Marburg Lung Center

University of Giessen and Marburg Lung Center Dept of Medicine Imperial College London London UK

References provided by Crossref.org

Long-Term Treatment With Subcutaneous Treprostinil in Patients With Severe Inoperable Chronic Thromboembolic Pulmonary Hypertension in the Multimodal Therapy Era (Data From CTREPH Study Open Label Extension)

Computed tomography angiographic parameters of pulmonary artery as prognostic factors of residual pulmonary hypertension after pulmonary endarterectomy

Riociguat in patients with chronic thromboembolic pulmonary hypertension: results from an early access study

Haemodynamic effects of riociguat in inoperable/recurrent chronic thromboembolic pulmonary hypertension