Nazzareno Galiè1, Friedrich Grimminger2, Ekkehard Grünig3, Marius M Hoeper4, Marc Humbert5, Zhi-Cheng Jing6, Anne M Keogh7, David Langleben8, Lewis J Rubin9, Arno Fritsch10, Neil Davie10, Hossein-Ardeschir Ghofrani11. 1. Department of Experimental, Diagnostic, and Specialty Medicine-DIMES, Bologna University Hospital, Bologna, Italy. Electronic address: nazzareno.galie@unibo.it. 2. University of Giessen and Marburg Lung Center, member of German Center for Lung Research, Giessen, Germany. 3. Centre for Pulmonary Hypertension, Thoraxclinic, University Hospital Heidelberg, Heidelberg, Germany. 4. Clinic for Respiratory Medicine, Hannover Medical School, member of German Center for Lung Research, Hannover, Germany. 5. 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. 6. State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. 7. Heart Transplant Unit, St. Vincent's Hospital, Sydney, New South Wales, Australia. 8. Center for Pulmonary Vascular Disease and Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada. 9. Pulmonary and Critical Care Division, University of California, San Diego, La Jolla, California. 10. Global Clinical Development, Bayer Pharma AG, Wuppertal, Germany. 11. University of Giessen and Marburg Lung Center, member of German Center for Lung Research, Giessen, Germany; Department of Medicine, Imperial College London, London, United Kingdom.
Abstract
BACKGROUND: Detailed hemodynamic data from the phase III PATENT-1 study of riociguat in patients with pulmonary arterial hypertension (PAH) were investigated. METHODS:Patients with PAH who were treatment naïve or pre-treated withendothelin receptor antagonists or non-intravenous prostanoids were randomly assigned to riociguat up to 2.5 mg 3 times a day or placebo. Hemodynamic parameters were assessed at baseline and week 12. RESULTS: Riociguat significantly decreased pulmonary vascular resistance in treatment-naïve (n = 221; least squares [LS] mean difference -266 dyne∙sec∙cm-5 [95% confidence interval (CI) -357 to -175; p < 0.0001]) and pre-treated (n = 222; LS mean difference -186 dyne∙sec ∙cm-5 [95% CI -252 to -120; p < 0.0001]) patients and significantly increased cardiac index (LS mean difference +0.7 [95% CI 0.5 to 0.8] and +0.5 [95% CI 0.3 to 0.7], respectively [both p < 0.0001]). Mean pulmonary artery pressure (p = 0.0056 and p = 0.0019 for treatment-naïve and pre-treated patients, respectively), mean arterial pressure (both p < 0.0001), and systemic vascular resistance (both p < 0.0001) were significantly reduced, and there was an increase in mixed venous oxygen saturation (p < 0.0001 and p = 0.0004, respectively). Results were similar in patients pre-treated with endothelin receptor antagonists and patients pre-treated with non-intravenous prostanoids. Improvements in 6-minute walking distance correlated very weakly with improvements in pulmonary vascular resistance (r = -0.21 [95% CI -0.30 to -0.11; p < 0.0001]) and cardiac index (r = 0.16 [95% CI 0.06 to 0.25; p < 0.0016]). CONCLUSIONS: Riociguat significantly improved hemodynamic parameters in pre-treated and treatment-naïve patients with PAH.
RCT Entities:
BACKGROUND: Detailed hemodynamic data from the phase III PATENT-1 study of riociguat in patients with pulmonary arterial hypertension (PAH) were investigated. METHODS:Patients with PAH who were treatment naïve or pre-treated with endothelin receptor antagonists or non-intravenous prostanoids were randomly assigned to riociguat up to 2.5 mg 3 times a day or placebo. Hemodynamic parameters were assessed at baseline and week 12. RESULTS:Riociguat significantly decreased pulmonary vascular resistance in treatment-naïve (n = 221; least squares [LS] mean difference -266 dyne∙sec∙cm-5 [95% confidence interval (CI) -357 to -175; p < 0.0001]) and pre-treated (n = 222; LS mean difference -186 dyne∙sec ∙cm-5 [95% CI -252 to -120; p < 0.0001]) patients and significantly increased cardiac index (LS mean difference +0.7 [95% CI 0.5 to 0.8] and +0.5 [95% CI 0.3 to 0.7], respectively [both p < 0.0001]). Mean pulmonary artery pressure (p = 0.0056 and p = 0.0019 for treatment-naïve and pre-treated patients, respectively), mean arterial pressure (both p < 0.0001), and systemic vascular resistance (both p < 0.0001) were significantly reduced, and there was an increase in mixed venous oxygen saturation (p < 0.0001 and p = 0.0004, respectively). Results were similar in patients pre-treated with endothelin receptor antagonists and patients pre-treated with non-intravenous prostanoids. Improvements in 6-minute walking distance correlated very weakly with improvements in pulmonary vascular resistance (r = -0.21 [95% CI -0.30 to -0.11; p < 0.0001]) and cardiac index (r = 0.16 [95% CI 0.06 to 0.25; p < 0.0016]). CONCLUSIONS:Riociguat significantly improved hemodynamic parameters in pre-treated and treatment-naïve patients with PAH.
Authors: Rodrigo Cartin-Ceba; Michael Halank; Hossein-Ardeschir Ghofrani; Marc Humbert; John Mattson; Arno Fritsch; Michael Krowka Journal: Pulm Circ Date: 2018-03-22 Impact factor: 3.017
Authors: Hossein-Ardeschir Ghofrani; Ekkehard Grünig; Pavel Jansa; David Langleben; Stephan Rosenkranz; Ioana R Preston; Franck Rahaghi; Namita Sood; Dennis Busse; Christian Meier; Marc Humbert Journal: Pulm Circ Date: 2020-07-16 Impact factor: 3.017