A proportion of pulmonary arterial hypertension (PAH) patients do not reach treatment goals with phosphodiesterase-5 inhibitors (PDE5i). RESPITE investigated the safety, feasibility and benefit of switching from PDE5i to riociguat in these patients.RESPITE was a 24-week, open-label, multicentre, uncontrolled study. Patients in World Health Organization (WHO) functional class (FC) III, with 6-min walking distance (6MWD) 165-440 m, cardiac index <3.0 L·min-1·m-2 and pulmonary vascular resistance >400 dyn·s·cm-5 underwent a 1-3 day PDE5i treatment-free period before receiving riociguat adjusted up to 2.5 mg maximum t.i.d Exploratory end-points included change in 6MWD, WHO FC, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and safety.Of 61 patients enrolled, 51 (84%) completed RESPITE. 50 (82%) were receiving concomitant endothelin receptor antagonists. At week 24, mean±sd 6MWD had increased by 31±63 m, NT-proBNP decreased by 347±1235 pg·mL-1 and WHO FC improved in 28 patients (54%). 32 patients (52%) experienced study drug-related adverse events and 10 (16%) experienced serious adverse events (2 (3%) study drug-related, none during the PDE5i treatment-free period). Six patients (10%) experienced clinical worsening, including death in two (not study drug-related).In conclusion, selected patients with PAH may benefit from switching from PDE5i to riociguat, but this strategy needs to be further studied.

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

Centre for Pulmonary Hypertension Thorax Clinic at the University Hospital Heidelberg Germany

Centre for Pulmonary Vascular Disease and Lady Davis Institute Jewish General Hospital McGill University Montreal QC Canada

Chrestos Concept GmbH and Co KG Essen Germany

Clinic 3 for Internal Medicine University of Cologne Cologne Germany

Clinic for Respiratory Medicine Hannover Medical School member of the German Centre for Lung Research Hannover Germany

Clinical Dept of Cardiology and Angiology 1st Faculty of Medicine 2nd Medical Dept Charles University Prague Czech Republic

Cologne Cardiovascular Research Centre University of Cologne Cologne Germany

Dept of Cardiology Erasme University Hospital Brussels Belgium

Dept of Medicine Imperial College London London UK

Division of Cardiology Fondazione Istituto di Ricerca e Cura a Carattere Scientifico Policlinico S Matteo Pavia Italy

Division of Pulmonary Sleep and Critical Care Medicine Rhode Island Hospital Alpert Medical School of Brown University Providence RI USA

Global Clinical Development Bayer HealthCare Pharmaceuticals Barcelona Spain

Global Medical Affairs Bayer Pharma AG Berlin Germany

Institute of Cellular Medicine Newcastle University Newcastle upon Tyne UK

Pulmonary Hypertension Unit Dept of Cardiovascular and Respiratory Disease 'La Sapienza' University of Rome Rome Italy

The Cardiovascular Institute Allegheny General Hospital Pittsburgh PA USA

University of Giessen and Marburg Lung Centre member of the German Centre for Lung Research Giessen Germany

Eur Respir J. 2017 Sep 9;50(3):1701527. doi: 10.1183/13993003.01527-2017. PubMed

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