title: Riociguat for the treatment of pulmonary arterial hypertension: a long-term extension study (PATENT-2).
abstract: Riociguat is a soluble, guanylate cyclase stimulator, approved for pulmonary arterial hypertension. In the 12-week PATENT-1 study, riociguat was well tolerated and improved several clinically relevant end-points in patients with pulmonary arterial hypertension who were treatment naïve or had been pretreated with endothelin-receptor antagonists or prostanoids. The PATENT-2 open-label extension evaluated the long-term safety and efficacy of riociguat. Eligible patients from the PATENT-1 study received riociguat individually adjusted up to a maximum dose of 2.5 mg three times daily. The primary objective was to assess the safety and tolerability of riociguat; exploratory efficacy assessments included 6-min walking distance and World Health Organization (WHO) functional class. Overall, 396 patients entered the PATENT-2 study and 324 (82%) were ongoing at this interim analysis (March 2013). The safety profile of riociguat in PATENT-2 was similar to that observed in PATENT-1, with cases of haemoptysis and pulmonary haemorrhage also being observed in PATENT-2. Improvements in the patients', 6-min walking distance and WHO functional class observed in PATENT-1 persisted for up to 1 year in PATENT-2. In the observed population at the 1-year time point, mean±sd 6-min walking distance had changed by 51±74 m and WHO functional class had improved in 33%, stabilised in 61% and worsened in 6% of the patients versus the PATENT-1 baseline. Long-term riociguat was well tolerated in patients with pulmonary arterial hypertension, and led to sustained improvements in exercise capacity and functional capacity for up to 1 year.
authors.affiliation: Dept of Medicine, University of California, San Diego, La Jolla, California, USA.
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Rubin
authors.affiliation: Dept of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna University Hospital, Bologna, Italy.
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Galiè
authors.affiliation: University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany Member of the German Center of Lung Research (DZL).
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: Université Paris-Sud, Le Kremlin-Bicêtre, France AP-HP Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis, Robinson, 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: St Vincent's Hospital, Sydney, Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Keogh
authors.affiliation: Center for Pulmonary Vascular Disease and Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Langleben
authors.affiliation: Global Clinical Development, Bayer HealthCare Pharmaceuticals, Wuppertal, Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Fritsch
authors.affiliation: Bayer HealthCare Pharmaceuticals, São Paulo, Brazil.
authors.forename: Flavia
authors.initials: F
authors.lastname: Menezes
authors.affiliation: Global Clinical Development, Bayer HealthCare Pharmaceuticals, Wuppertal, Germany.
authors.forename: Neil
authors.initials: N
authors.lastname: Davie
authors.affiliation: University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany Member of the German Center of Lung Research (DZL) Dept of Medicine, Imperial College London, London, UK.
authors.forename: Hossein-Ardeschir
authors.initials: HA
authors.lastname: Ghofrani
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D004311:Double-Blind Method; D065128:Endothelin Receptor Antagonists / Q000627:therapeutic use; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D011453:Prostaglandins / Q000737:chemistry; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011788:Quality of Life; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D011453:Prostaglandins; D011720:Pyrazoles; D011743:Pyrimidines; D006162:Guanylate Cyclase; C542595:riociguat