BACKGROUND: RESPITE evaluated patients with pulmonary arterial hypertension and an inadequate response to phosphodiesterase type 5 inhibitors (PDE5i) who switched to riociguat. This post hoc analysis assessed response to this switch in parameters associated with clinical improvement. METHODS: RESPITE was a 24-week, uncontrolled pilot study (n = 61). Differences in functional, hemodynamic, and cardiac function parameters, REVEAL risk score (RRS), and biomarkers were compared between responders (free from clinical worsening, World Health Organization functional class I/II, and ≥30 m improvement in 6-min walking distance at Week 24) and non-responders. RESULTS: Of 51 patients (84%) completing RESPITE, 16 (31%) met the responder endpoint. At baseline, there were significant differences between responders and non-responders in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), growth/differentiation factor 15 (GDF-15), and RRS, whereas there were no differences in hemodynamics or cardiac function. At Week 24, responders had significant improvements in pulmonary arterial compliance, pulmonary vascular resistance, and mean pulmonary arterial pressure, while non-responders showed no significant change. Cardiac efficiency and stroke volume index significantly improved irrespective of responder status. CONCLUSIONS: NT-proBNP, GDF-15, and RRS were identified as potential predictors of response in patients switching from PDE5i to riociguat. Further prospective controlled studies are needed to confirm the association of these parameters with response.

Assistance Publique Hôspitaux de Paris Service de Pneumologie Hôpital Bicêtre Université Paris Sud Laboratoire d Excellence en Rescherche sur le Médicament et Innovation Thérapeutique and INSERM Unité 999 Le Kremlin Bicêtre France

Bayer AG Berlin Germany

Center 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 Center for Lung Research Hannover Germany

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

Department of Cardiology Erasme University Hospital Brussels Belgium

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

Division of Cardiology University of Minnesota Minneapolis MN USA

Division of Cardiovascular Medicine The Ohio State University Wexner Medical Center OH USA

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

Institute of Cellular Medicine Newcastle University Newcastle upon Tyne UK

The Cardiovascular Institute Allegheny General Hospital Pittsburgh PA USA

University of Giessen and Marburg Lung Center Member of the German Center for Lung Research Giessen Germany; Department of Medicine Imperial College London London UK

Int J Cardiol. 2021 Jun 15;333:210. doi: 10.1016/j.ijcard.2021.03.004. PubMed

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