BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, debilitating, and life-threatening disease. We investigated associations between markers of disease severity and long-term outcomes in patients with inoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy (PEA) who were receiving the soluble guanylate cyclase stimulator riociguat. We also present safety and efficacy from the final data cutoff of CHEST-2, where most patients had received riociguat for at least 2 years. METHODS: Eligible patients from the CHEST-1 study entered the CHEST-2 open-label extension study, in which all patients received riociguat individually adjusted to a maximum dose of 2·5 mg three times per day. The primary endpoint was safety and tolerability. We did exploratory assessments of associations between markers of disease severity (6-min walking distance [6MWD], N-terminal prohormone of brain natriuretic peptide [NT-proBNP] concentration, and WHO functional class) at baseline and follow-up with overall survival and clinical worsening-free survival. We used Kaplan-Meier and Cox proportional hazards analyses. CHEST-2 is registered at ClinicalTrials.gov, number NCT00910429. FINDINGS: 237 patients entered CHEST-2. At 2 years, overall survival was 93% (95% CI 89-96) and clinical worsening-free survival was 82% (77-87). A significant association with overall survival was seen for 6MWD and NT-proBNP concentration at baseline (p=0·0199 and p=0·0183, respectively) and at follow-up (p=0·0385 and p=0·0068, respectively). Change from baseline in 6MWD was also significantly associated with survival (p=0·0047). WHO functional class at baseline and follow-up showed no significant association with overall survival but was associated with clinical worsening-free survival. Riociguat was well tolerated by most patients and no new safety signals were identified. Serious adverse events were seen in 129 (54%) of 237 patients, and 14 (6%) discontinued riociguat therapy because of adverse events. INTERPRETATION: Riociguat may be used long term in patients with CTEPH. 6MWD and NT-proBNP concentration are good prognostic markers. FUNDING: Bayer Pharma AG.

Assistance Publique Hôpitaux de Paris Service de Pneumologie Hôpital Bicêtre Université Paris Sud Laboratoire d'Excellence en Recherche sur le Médicament et Innovation Thérapeutique Le Kremlin Bicêtre France; INSERM Unité 999 l'Hopital Bicêtre Le Kremlin Bicêtre France

Beijing Institute of Respiratory Medicine Beijing Chao Yang Hospital Beijing China; Department of Respiratory Medicine Capital Medical University Beijing China; Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders Beijing China

Clinical Department of Cardiology and Angiology of the 1st Faculty of Medicine and General Teaching Hospital Prague Czech Republic

Division of Cardiothoracic Surgery Foundation 1 R C C S Policlinico San Matteo University of Pavia School of Medicine Pavia Italy

Division of Pulmonary and Critical Care Medicine School of Medicine University of California San Diego La Jolla CA USA

German Centre of Lung Research Giessen Germany; Clinic for Respiratory Medicine Hannover Medical School Hannover Germany

Global Clinical Development Bayer HealthCare Pharmaceuticals Wuppertal Germany

Global Clinical Development Bayer Pharma AG Barcelona Spain

Global Clinical Development Bayer Pharma AG Berlin Germany

Kerckhoff Heart and Lung Centre Bad Nauheim Germany

National Heart Institute Cardiopulmonary Department Mexico City Mexico

University of Giessen and Marburg Lung Centre Giessen Germany

University of Giessen and Marburg Lung Centre Giessen Germany; Department of Medicine Imperial College London London UK

Lancet Respir Med. 2016 May;4(5):338-9. doi: 10.1016/S2213-2600(16)30041-8. PubMed

Citace poskytuje Crossref.org

Riociguat in patients with chronic thromboembolic pulmonary hypertension: results from an early access study

Zobrazit více v PubMed

ClinicalTrials.gov
NCT00910429