OBJECTIVE: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. METHODS: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits (usually every 3-6 months) and collated via case report forms. RESULTS: In total, 326 patients with PAH were included in the analysis. The most common AEs in these patients were dizziness (11.7%), right ventricular (RV)/cardiac failure (10.7%), edema/peripheral edema (10.7%), diarrhea (8.6%), dyspnea (8.0%), and cough (7.7%). The most common SAEs were RV/cardiac failure (10.1%), pneumonia (6.1%), dyspnea (4.0%), and syncope (3.4%). The exposure-adjusted rate of hemoptysis/pulmonary hemorrhage was 2.5 events per 100 patient-years. CONCLUSION: Final data from EXPERT show that in patients with PAH, the safety of riociguat in clinical practice was consistent with clinical trials, with no new safety concerns identified and a lower exposure-adjusted rate of hemoptysis/pulmonary hemorrhage than in the long-term extension of the Phase 3 trial in PAH.

2nd Department of Critical Care University Hospital Attikon National and Kapodistrian University of Athens Athens Greece

Alberta Health Services University of Calgary Calgary Alberta Canada

Bayer AG Global Development Global Medical Affairs Berlin Germany

Center for Pulmonary Vascular Disease Jewish General Hospital McGill University Montreal Quebec Canada

Centre for Pulmonary Hypertension Thoraxclinic at Heidelberg University Hospital Heidelberg Germany

Clinic of Pulmonology University Hospital Zurich Zurich Switzerland

Clinical Department of Respiratory Diseases University Hospitals and Laboratory of Respiratory Diseases and Thoracic Surgery KU Leuven University of Leuven Leuven Belgium

Département de Cardiologie Cliniques Universitaires de Bruxelles Hôpital Erasme Brussels Belgium

Department 3 of Internal Medicine and Cologne Cardiovascular Research Center Cologne University Heart Center Cologne Germany

Department of Cardiology 1 Aristotle University of Thessaloniki Thessaloniki Greece

Department of Cardiology and Angiology Faculty of Medicine Slovak Medical University and National Institute of Cardiovascular Diseases Bratislava Slovak Republic

Department of Cardiology Hospital 12 de Octubre CIBER CV Madrid Spain

Department of Internal Medicine 2 Division of Pneumology University Medical Center Regensburg Germany

Department of Medicine Department of Cardiovascular Medicine Charles University Prague Prague Czech Republic

Department of Pneumology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Pulmonology St Antonius Ziekenhuis Nieuwegein the Netherlands

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

Department of Respiratory Medicine University of Leipzig Leipzig Germany

Division of Cardiology Department of Medicine University of Ottawa Heart Institute Ottawa Ontario Canada

German Rheumatism Research Center Berlin Leibniz Institute Berlin Germany

Hospital Clínic IDIBAPS University of Barcelona Barcelona Spain; Biomedical Research Networking Center on Respiratory Diseases Madrid Spain

Institute for Clinical Pharmacology Technical University Dresden Germany

Medical Clinic 1 Department of Pneumology University Hospital Carl Gustav Carus Dresden Germany

Pulmonary Vascular Disease Unit Royal Papworth Hospital Cambridge UK

Respiratory Department Ramón y Cajal University Hospital Madrid Spain

Servicestelle für Klinische Studien Krankenhaus der Elisabethinen Linz GmbH Linz Austria

Université Paris Saclay Inserm U999 Service de Pneumologie et Soins Intensifs Respiratoires Hôpital Bicêtre Le Kremlin Bicêtre France

Université Paris Sud Le Kremlin Bicêtre Service de Pneumologie Centre de Référence de l'Hypertension Pulmonaire Sévère DHU Thorax Innovation Hôpital Bicêtre Le Kremlin Bicêtre Paris France

University of Giessen and Marburg Lung Center Germany

VU Medisch Centrum Amsterdam the Netherlands

References provided by Crossref.org