title: Riociguat for pulmonary arterial hypertension associated with congenital heart disease.
abstract: OBJECTIVE
  The Pulmonary Arterial hyperTENsion sGC-stimulator Trial-1 (PATENT-1) was a randomised, double-blind, placebo-controlled phase III trial evaluating riociguat in patients with pulmonary arterial hypertension (PAH). PATENT-2 was an open-label long-term extension to PATENT-1. Here, we explore the efficacy and safety of riociguat in the subgroup of patients with persistent/recurrent PAH after correction of congenital heart disease (PAH-CHD) from the PATENT studies.
  
  
  METHODS
  In PATENT-1, patients received riociguat (maximum 2.5 or 1.5 mg three times daily) or placebo for 12 weeks; efficacy assessments included change from baseline to study end in 6-min walking distance (6MWD; primary), pulmonary vascular resistance (PVR), N-terminal of the prohormone of brain natriuretic peptide (NT-proBNP), WHO functional class (WHO FC) and time to clinical worsening. In PATENT-2, eligible patients from PATENT-1 received long-term riociguat (maximum 2.5 mg three times daily); the primary assessment was safety and tolerability. All PAH-CHD patients had a corrected cardiac defect.
  
  
  RESULTS
  In PATENT-1, riociguat increased mean±SD 6MWD from baseline to week 12 by 39±60 m in patients with PAH-CHD versus 0±42 m for placebo. Riociguat also improved several secondary variables versus placebo, including PVR (-250±410 vs -66±632 dyn·s/cm(5)), NT-proBNP (-164±317 vs -46±697 pg/mL) and WHO FC (21%/79%/0% vs 8%/83%/8% improved/stabilised/worsened). One patient experienced clinical worsening (riociguat 1.5 mg group). Riociguat was well tolerated. In PATENT-2, riociguat showed sustained efficacy and tolerability in patients with PAH-CHD at 2 years.
  
  
  CONCLUSIONS
  Riociguat was well tolerated in patients with PAH-CHD and improved clinical outcomes including 6MWD, PVR, WHO FC and NT-proBNP.
  
  
  BACKGROUND
  The clinical trials numbers are NCT00810693 for PATENT-1 and NCT00863681 for PATENT-2.
authors.affiliation: Department III of Internal Medicine and Cologne Cardiovascular Research Center (CCRC), Cologne University Heart Center, Cologne, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Rosenkranz
authors.affiliation: University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany, and Member of the German Center of Lung Research (DZL) Department of Medicine, Imperial College London, London, UK.
authors.forename: Hossein-Ardeschir
authors.initials: HA
authors.lastname: Ghofrani
authors.affiliation: Pediatric Cardiology Unit, Children's Hospital, University of Geneva, Geneva, Switzerland.
authors.forename: Maurice
authors.initials: M
authors.lastname: Beghetti
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, Colorado, USA.
authors.forename: Dunbar
authors.initials: D
authors.lastname: Ivy
authors.affiliation: Bayer Pharma AG, Wuppertal, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Frey
authors.affiliation: Bayer Pharma AG, Wuppertal, Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Fritsch
authors.affiliation: Bayer Pharma AG, Wuppertal, Germany.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Weimann
authors.affiliation: Pediatric Heart Centre, University Children's Hospital, Giessen, Germany.
authors.forename: Soundos
authors.initials: S
authors.lastname: Saleh
authors.affiliation: Pediatric Heart Centre, University Children's Hospital, Giessen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Apitz
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006330:Heart Defects, Congenital / Q000150:complications*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy*; D008297:Male; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D011720:Pyrazoles; D011743:Pyrimidines; C542595:riociguat