Riociguat treatment in patients with pulmonary arterial hypertension: Final safety data from the EXPERT registry
Marius M. Hoeper, Miguel-Angel Gomez Sanchez, Marc Humbert, David Pittrow, Gérald Simonneau, Henning Gall, Ekkehard Grünig, Hans Klose, Michael Halank, David Langleben, Repke J. Snijder, Pilar Escribano Subías, Lisa Mielniczuk, Tobias Lange, Jean‐Luc Vachiéry, Hubert Wirtz, Douglas Helmersen, Iraklis Tsangaris, Joan Albert Barberà, Joanna Pepke‐Żaba, Anco Boonstra, Stephan Rosenkranz, Silvia Ulrich, Regina Steringer‐Mascherbauer, Marion Delcroix, Pavel Jansa, Iveta Šimková, George Giannakoulas, Jens Klotsche, Evgenia Williams, Christian Meier, Hossein-Ardeschir Ghofrani, Jorge Cáneva, Graciela Tuhay, Mirta Díez, María L. Talavera, Adriana Acosta, Norberto Vulcano, Martín Bosio, Lorena Maldonado, Sabino Deleo, Luciano Melatini, Anne Keogh, Eugene Kotlyar, John Feenstra, Nathan Dwyer, Heath Adams, Wendy Stevens, Peter Steele, Susanna Proudman, Robert Minson, Glenn Reeves, Melanie Lavender, Benjamin Ng, Michele Mackenzie, Lisa C. Barry, Margarethe Gruenberger, Charlotte Huber, Iréne Lang, Ioana Tilea, Roela Sadushi‐Kolici, Judith Löffler‐Ragg, Lisa-Theresa Feistmantl, P Evrard, Julien Guiot, Marco Naldi, Michel De Pauw, Renaud Louis, Sanjay Mehta, Rafael Conde Camacho, Patricia Parada Tovar, Alejandro Londoño, Felipe Campo, Paula Andrea Gaviria García, Camila Lema, Mauricio Orozco‐Levi, William Martínez, Juan Esteban Gomez, Jens Erik Nielsen‐Kudsk, Søren Mellemkjær, Ly Anton, Alan Altraja, Tapani Vihinen, Tuija Vasankari, Olivier Sitbon, Vincent Cottin, L. Têtu, Elise Noël‐Savina, Nicole Shearman, Susanne Tayler, Ilona Olzik, Christine Kulka, Jan Grimminger, Marcel Simon, Anna Nolde, Tim Oqueka, Lars Harbaum, Benjamin Egenlauf, Ralf Ewert, Christian Schulz
Abstract
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.