title: Comparison of hemodynamic parameters in treatment-naïve and pre-treated patients with pulmonary arterial hypertension in the randomized phase III PATENT-1 study.
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 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.affiliation: Department of Experimental, Diagnostic, and Specialty Medicine-DIMES, Bologna University Hospital, Bologna, Italy. Electronic address: nazzareno.galie@unibo.it.
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Galiè
authors.affiliation: University of Giessen and Marburg Lung Center, member of German Center for Lung Research, Giessen, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grimminger
authors.affiliation: Centre for Pulmonary Hypertension, Thoraxclinic, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Grünig
authors.affiliation: Clinic for Respiratory Medicine, Hannover Medical School, member of German Center for Lung Research, Hannover, Germany.
authors.forename: Marius M
authors.initials: MM
authors.lastname: Hoeper
authors.affiliation: 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.
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Jing
authors.affiliation: Heart Transplant Unit, St. Vincent's Hospital, Sydney, New South Wales, Australia.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Keogh
authors.affiliation: Center for Pulmonary Vascular Disease and Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Langleben
authors.affiliation: Pulmonary and Critical Care Division, University of California, San Diego, La Jolla, California.
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Rubin
authors.affiliation: Global Clinical Development, Bayer Pharma AG, Wuppertal, Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Fritsch
authors.affiliation: Global Clinical Development, Bayer Pharma AG, Wuppertal, Germany.
authors.forename: Neil
authors.initials: N
authors.lastname: Davie
authors.affiliation: 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.
authors.forename: Hossein-Ardeschir
authors.initials: HA
authors.lastname: Ghofrani
mesh_terms: D000284:Administration, Oral; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D065128:Endothelin Receptor Antagonists / Q000008:administration & dosage; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy*; D038622:Internationality; D008297:Male; D020714:Maximum Tolerated Dose; D011446:Prospective Studies; D011453:Prostaglandins / Q000008:administration & dosage; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D012016:Reference Values; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D065128:Endothelin Receptor Antagonists; D011453:Prostaglandins; D011720:Pyrazoles; D011743:Pyrimidines; C542595:riociguat
keywords: clinical trial; pulmonary; pulmonary arterial hypertension; riociguat; soluble guanylate cyclase stimulator