Universität zu Köln

Klinger, James R., Chakinala, Murali M., Langleben, David, Rosenkranz, Stephan and Sitbon, Olivier . Riociguat: Clinical research and evolving role in therapy. Br. J. Clin. Pharmacol.. HOBOKEN: WILEY. ISSN 1365-2125

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Abstract

Riociguat is a first-in-class soluble guanylate cyclase stimulator, approved for the treatment of adults with pulmonary arterial hypertension (PAH), inoperable chronic thromboembolic pulmonary hypertension (CTEPH), or persistent or recurrent CTEPH after pulmonary endarterectomy. Approval was based on the results of the phase III PATENT-1 (PAH) and CHEST-1 (CTEPH) studies, with significant improvements in the primary endpoint of 6-minute walk distance vs placebo of +36 m and +46 m, respectively, as well as improvements in secondary endpoints such as pulmonary vascular resistance and World Health Organization functional class. Riociguat acts as a stimulator of cyclic guanosine monophosphate synthesis rather than as an inhibitor of cGMP metabolism. As with other approved therapies for PAH, riociguat has antifibrotic, antiproliferative and anti-inflammatory effects, in addition to vasodilatory properties. This has led to further clinical studies in patients who do not achieve a satisfactory clinical response with phosphodiesterase type-5 inhibitors. Riociguat has also been evaluated in patients with World Health Organization group 2 and 3 pulmonary hypertension, and other conditions including diffuse cutaneous systemic sclerosis, Raynaud's phenomenon and cystic fibrosis. This review evaluates the results of the original clinical trials of riociguat for the treatment of PAH and CTEPH, and summarises the body of work that has examined the safety and efficacy of riociguat for the treatment of other types of pulmonary hypertension.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Klinger, James R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Chakinala, Murali M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Langleben, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Rosenkranz, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Sitbon, Olivier UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-307315
DOI:	10.1111/bcp.14676
Journal or Publication Title:	Br. J. Clin. Pharmacol.
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1365-2125
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SOLUBLE GUANYLATE-CYCLASE; PULMONARY ARTERIAL-HYPERTENSION; LONG-TERM EXTENSION; RESPONDER THRESHOLD CRITERIA; INTERSTITIAL LUNG-DISEASE; HEART-FAILURE; NITRIC-OXIDE; RISK SCORE; OPEN-LABEL; PHOSPHODIESTERASE-5 INHIBITION Multiple languages Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/30731