title: Use of responder threshold criteria to evaluate the response to treatment in the phase III CHEST-1 study.
abstract: BACKGROUND
  In the Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase - Stimulator Trial 1 (CHEST-1) study, riociguat improved 6-minute walking distance (6MWD) vs placebo in patients with inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy. In this study, the proportion of patients who achieved responder thresholds that correlate with improved outcome in patients with pulmonary arterial hypertension was determined at baseline and at the end of CHEST-1.
  
  
  METHODS
  Patients received placebo or riociguat individually adjusted up to 2.5 mg 3 times a day for 16 weeks. Response criteria were defined as follows: 6MWD increase ≥40 m, 6MWD ≥380 m, cardiac index ≥2.5 liters/min/m(2), pulmonary vascular resistance <500 dyn∙sec∙cm(-5), mixed venous oxygen saturation ≥65%, World Health Organization functional class I/II, N-terminal pro-brain natriuretic peptide <1,800 pg/ml, and right atrial pressure <8 mm Hg.
  
  
  RESULTS
  Riociguat increased the proportion of patients with 6MWD ≥380 m, World Health Organization functional class I/II, and pulmonary vascular resistance <500 dyn∙sec∙cm(-5) from 37%, 34%, and 25% at baseline to 58%, 57%, and 50% at Week 16, whereas there was little change in placebo-treated patients (6MWD ≥380 m, 43% vs 44%; World Health Organization functional class I/II, 29% vs 38%; pulmonary vascular resistance <500 dyn∙sec∙cm(-5), 27% vs 26%). Similar changes were observed for thresholds for cardiac index, mixed venous oxygen saturation, N-terminal pro-brain natriuretic peptide, and right atrial pressure.
  
  
  CONCLUSIONS
  In this exploratory analysis, riociguat increased the proportion of patients with inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy achieving criteria defining a positive response to therapy.
authors: Division of Cardiothoracic Surgery, Foundation "I.R.C.C.S. Policlinico San Matteo," University of Pavia School of Medicine, Pavia, Italy. Electronic address: darmini@smatteo.pv.it.
authors: Andrea M
authors: AM
authors: D'Armini
authors: University of Giessen and Marburg Lung Center, UGMLC, Giessen, Germany, member of the German Center of Lung Research (DZL); Department of Medicine, Imperial College London, London, United Kingdom.
authors: Hossein-Ardeschir
authors: HA
authors: Ghofrani
authors: Division of Pulmonary and Critical Care Medicine, University of California San Diego School of Medicine, San Diego, California.
authors: Nick H
authors: NH
authors: Kim
authors: Kerckhoff Heart and Lung Center, Bad Nauheim, Germany.
authors: Eckhard
authors: E
authors: Mayer
authors: Division of Cardiothoracic Surgery, Foundation "I.R.C.C.S. Policlinico San Matteo," University of Pavia School of Medicine, Pavia, Italy.
authors: Marco
authors: M
authors: Morsolini
authors: National Heart Institute, Mexico City, Mexico.
authors: Tomás
authors: T
authors: Pulido-Zamudio
authors: 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 INSERM Unité 999, Le Kremlin-Bicêtre, France.
authors: Gerald
authors: G
authors: Simonneau
authors: National Institute for Health Research/Wellcome Trust Imperial Clinical Research Facility, Imperial Centre for Translational and Experimental Medicine, Imperial College London, London, United Kingdom.
authors: Martin R
authors: MR
authors: Wilkins
authors: Global Development, Bayer plc, Newbury, United Kingdom.
authors: John
authors: J
authors: Curram
authors: Global Clinical Development, Bayer Pharma AG, Wuppertal, Germany.
authors: Neil
authors: N
authors: Davie
authors: Clinic for Respiratory Medicine, Hannover Medical School, Hannover, Germany, and Member of the German Centre of Lung Research (DZL).
authors: Marius M
authors: MM
authors: Hoeper
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014655:Vascular Resistance; D016278:Ventricular Function, Right / Q000187:drug effects / Q000502:physiology*; D017725:Ventricular Pressure / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D011720:Pyrazoles; D011743:Pyrimidines; C542595:riociguat
keywords: chronic thromboembolic pulmonary hypertension; responder threshold criteria; riociguat; soluble guanylate cyclase stimulator; treatment response