title: Riociguat: a novel therapeutic option for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.
abstract: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are serious and often fatal diseases. The pathophysiology of both diseases is complex and in part is attributed to alterations in the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate pathway. Riociguat, a novel sGC stimulator, acts on this pathway through a dual mechanism of action by directly stimulating sGC in a NO-independent manner and also increasing the sensitivity of sGC to NO. Based on benefits from clinical trials for both PAH and CTEPH, riociguat was approved by Health Canada and the US Food and Drug Administration as the first medical therapy for patients with CTEPH who are deemed inoperable or have residual/recurrent PH after pulmonary endarterectomy (PEA), and as a novel treatment option for patients with PAH. This article reviews the key findings from the phase III trials for riociguat that led to these approvals and the implications this has for the treatment of patients with PAH and CTEPH.
authors.affiliation: Department of Medicine, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Onatrio, Canada. Electronic address: lmielniczuk@ottawaheart.ca.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Mielniczuk
authors.affiliation: Department of Medicine, Division of Respiratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: John R
authors.initials: JR
authors.lastname: Swiston
authors.affiliation: Pulmonary Hypertension Association (PHA) Canada, Canada; Southwest Ontario PH Clinic, London Health Sciences Centre, London, Ontario, Canada; Division of Respirology, Department of Medicine, Schulich School of Medicine, Western University, London, Ontario, Canada.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mehta
mesh_terms: D000818:Animals; D002908:Chronic Disease; D017326:Clinical Trials, Phase III as Topic; D065627:Familial Primary Pulmonary Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D011655:Pulmonary Embolism / Q000150:complications; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*
chemical_list: D011720:Pyrazoles; D011743:Pyrimidines; C542595:riociguat