CHEST Guidelines-Riociguat--Mode-of-Action-and-Clinical-Development

Riociguat--Mode-of-Action-and-Clinical-Development

Pdf Summary

Riociguat is a novel medication developed for treating pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), diseases marked by high pulmonary artery pressure leading to heart failure if untreated. Acting as a soluble guanylate cyclase (sGC) stimulator, riociguat works by enhancing the nitric oxide-sGC-cyclic guanosine monophosphate (cGMP) pathway, overcoming limitations of other treatments that depend on nitric oxide (NO) levels alone.<br /><br />Several pivotal studies have demonstrated the efficacy of riociguat. In phase II and III trials such as CHEST-1 and PATENT-1, riociguat significantly improved exercise capacity, pulmonary hemodynamics, and quality of life for patients both with and without previous treatments. The trials showed notable improvements in 6-minute walking distance and decreases in pulmonary vascular resistance and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, affirming its promise in clinical use.<br /><br />Riociguat displays a dual mode of action, increasing sGC activity both in the presence and absence of NO, distinguishing it from phosphodiesterase-5 inhibitors which solely prevent cGMP degradation. This action makes it particularly beneficial for patients with compromised NO production.<br /><br />Currently, riociguat is recommended as a first-line and add-on therapy for PAH and as the sole pharmacotherapy in inoperable or recurrent CTEPH cases post-surgery. Its administration is adjusted based on patient tolerance, typically starting at 1 mg three times daily, increasing to 2.5 mg based on blood pressure response.<br /><br />Despite its advantages, riociguat is contraindicated with PDE5 inhibitors or nitrates due to potential adverse interactions. Its side effects are generally manageable, with common ones being headache and dizziness.<br /><br />By addressing the NO-cGMP signaling deficiency central to PAH pathogenesis, riociguat provides a valuable new option that may also benefit patients unresponsive to existing therapies, necessitating further research to optimize its use.

Keywords

riociguat

pulmonary arterial hypertension

chronic thromboembolic pulmonary hypertension

soluble guanylate cyclase

nitric oxide

cGMP pathway

clinical trials

exercise capacity

pharmacotherapy

contraindications