OBJECTIVE: We compared the haemodynamic effects of riociguat in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent/recurrent CTEPH after pulmonary endarterectomy in the Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Trial 1 study. METHODS: Patients with inoperable or persistent/recurrent CTEPH (n=261; mean± SD age 59±14 years; 66% women) were randomised to riociguat (up to 2.5 mg three times daily) or placebo. Haemodynamic parameters were assessed at baseline and week 16. RESULTS: Riociguat decreased pulmonary vascular resistance (PVR) in inoperable (n=189; least-squares mean difference: -285 dyn s/cm5 (95% CI -357 to -213); p<0.0001) and persistent/recurrent (n=72; -131 dyn s/cm5 (95% CI -214 to -48); p=0.0025) patients. Cardiac index improved in inoperable patients by a least-squares mean difference of +0.6 L/min/m2 (95% CI 0.4 to 0.7; p<0.0001), while in persistent/recurrent patients the change was +0.2 L/min/m2 (95% CI -0.1 to 0.5; p=0.17). Mean pulmonary artery pressure decreased in inoperable and persistent/recurrent patients(-4.7 mm Hg (95% CI -6.9 to -2.6; p<0.0001 and -4.8 mm Hg (-8.2 to -1.5; p=0.0055), respectively). For all patients, changes in 6 min walk distance correlated with changes in PVR (r=-0.29 (95% CI -0.41 to -0.17); p<0.0001) and cardiac index (r=0.23 (95% CI 0.10 to 0.35); p=0.0004). CONCLUSIONS: Riociguat improved haemodynamics in patients with inoperable CTEPH or persistent/recurrent CTEPH. TRIAL REGISTRATION NUMBER: NCT00855465.

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 Institut National de la Santé et de la Recherche Médicale Unité 999 Le Kremlin Bicêtre France

Center for Pulmonary Hypertension Thoraxclinic University Hospital Heidelberg Heidelberg Germany

Clinic for Respiratory Medicine Hannover Medical School Hannover Germany

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

Department of Medicine Imperial College London London UK

Department of Pulmonary Circulation and Thromboembolic Diseases Medical Center of Postgraduate Education Europejskie Centrum Zdrowia Otwock Otwock Poland

Department of Respiratory Medicine Beijing Institute of Respiratory Medicine Beijing Chao Yang Hospital Capital Medical University Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders Beijing China

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 University of California San Diego La Jolla California USA

Division of Pulmonary Diseases Ludwig Maximilians University Munich Germany

German Center of Lung Research Giessen Germany

Global Clinical Development Bayer Pharma AG Wuppertal Germany

Kerckhoff Heart and Lung Center Bad Nauheim Germany

University of Giessen and Marburg Lung Center Giessen Germany

Am J Respir Crit Care Med. 2018 Aug 15;198(4):521-523. doi: 10.1164/rccm.201703-0659RR. PubMed

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