Riociguat: Mode of Action and Clinical Development in Pulmonary Hypertension

Chest. 2017 Feb;151(2):468-480. doi: 10.1016/j.chest.2016.05.024. Epub 2016 Jun 2.


Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are progressive and debilitating diseases characterized by gradual obstruction of the pulmonary vasculature, leading to elevated pulmonary artery pressure (PAP) and increased pulmonary vascular resistance (PVR). If untreated, they can result in death due to right-sided heart failure. Riociguat is a novel soluble guanylate cyclase (sGC) stimulator that is approved for the treatment of PAH and CTEPH. We describe in detail the role of the nitric oxide-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway in the pathogenesis of PAH and CTEPH and the mode of action of riociguat. We also review the preclinical data associated with the development of riociguat, along with the efficacy and safety data of riociguat from initial clinical trials and pivotal phase III randomized clinical trials in PAH and CTEPH.

Keywords: chronic thromboembolic pulmonary hypertension; pulmonary arterial hypertension; sGC stimulator.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chronic Disease
  • Cyclic GMP / metabolism
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / etiology
  • Hypertension, Pulmonary / metabolism
  • Nitric Oxide / metabolism
  • Pulmonary Embolism / complications
  • Pyrazoles / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Signal Transduction
  • Treatment Outcome
  • Walk Test


  • Pyrazoles
  • Pyrimidines
  • Nitric Oxide
  • Cyclic GMP
  • riociguat