{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T07:00:58Z","timestamp":1782284458170,"version":"3.54.5"},"reference-count":55,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,7,4]],"date-time":"2019-07-04T00:00:00Z","timestamp":1562198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Current treatment of pulmonary arterial hypertension (PAH) targets three signalling pathways: the nitric oxide (NO) pathway, the endothelin pathway and the prostacyclin pathway. Riociguat is a soluble guanylate cyclase stimulator, acting via the NO pathway in a new way: unlike other common drugs targeting this pathway (eg tadalafil and sildenafil), riociguat acts independently of endogenous NO. This MiniReview focuses on PAH treatment with riociguat and on its advantages and disadvantages compared with other drugs targeting the NO pathway. In the <jats:italic>PATENT\u20101<\/jats:italic> trial (NCT00810693), riociguat improved significantly the 6\u2010minute walking distance in patients suffering from PAH, with a mean difference (MD) of 36\u00a0m compared with a placebo group. The results are comparable to those found for its competitors tadalafil (MD of 33\u00a0m) and sildenafil (MD of 50\u00a0m) in the <jats:italic>PHIRST\u20101<\/jats:italic> trial <jats:italic>(<\/jats:italic>NCT00125918) and the <jats:italic>SUPER\u20101<\/jats:italic> trial (NCT00644605). No obvious advantages were found regarding pharmacokinetic features and adverse events. In the <jats:italic>RESPITE<\/jats:italic> study (NCT02007629), patients with PAH with insufficient response to treatment with tadalafil or sildenafil were switched to riociguat. These results indicate that riociguat might be superior regarding efficacy to PDE\u20105 inhibitors in a patient group, where endogenous NO production might be insufficient. This finding was further examined in the <jats:italic>REPLACE<\/jats:italic> study (NCT02891850). Moreover, riociguat has shown promising anti\u2010proliferative, anti\u2010inflammatory and anti\u2010fibrotic effects in animal models. Further investigations are needed to determine whether this applies also to human beings. Taken together, riociguat induces vasodilation of the pulmonary arteries and leads to an improvement in the ability to carry out physical activity.<\/jats:p>","DOI":"10.1111\/bcpt.13272","type":"journal-article","created":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T15:58:27Z","timestamp":1560787107000},"page":"202-214","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["A focus on riociguat in the treatment of pulmonary arterial hypertension"],"prefix":"10.1111","volume":"125","author":[{"given":"Anne Kathrine","family":"Toxvig","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Pharmacology Aarhus University Aarhus C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Wehland","sequence":"additional","affiliation":[{"name":"Clinic for Plastic, Aesthetic and Hand Surgery Otto von Guericke University Magdeburg Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Grimm","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Pharmacology Aarhus University Aarhus C Denmark"},{"name":"Department of Microgravity and Translational Regenerative Medicine, Faculty of Medicine and Mechanical Engineering Otto von Guericke University Magdeburg Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Infanger","sequence":"additional","affiliation":[{"name":"Clinic for Plastic, Aesthetic and Hand Surgery Otto von Guericke University Magdeburg Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Clinic for Plastic, Aesthetic and Hand Surgery Otto von Guericke University Magdeburg Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,4]]},"reference":[{"issue":"11","key":"e_1_2_4_2_1","first-page":"749","article-title":"Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension","volume":"39","author":"Khaybullina D","year":"2014","journal-title":"P T."},{"key":"e_1_2_4_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.10.029"},{"key":"e_1_2_4_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv317"},{"key":"e_1_2_4_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.10.032"},{"key":"e_1_2_4_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12623"},{"key":"e_1_2_4_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccl.2016.04.001"},{"key":"e_1_2_4_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acvd.2016.03.004"},{"key":"e_1_2_4_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.10.002"},{"key":"e_1_2_4_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2009.02120.x"},{"key":"e_1_2_4_11_1","doi-asserted-by":"publisher","DOI":"10.4103\/0976-500X.149151"},{"key":"e_1_2_4_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/17476348.2017.1317599"},{"key":"e_1_2_4_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe1306684"},{"key":"e_1_2_4_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2017.06.012"},{"key":"e_1_2_4_15_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S6208"},{"key":"e_1_2_4_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-016-0645-6"},{"issue":"1","key":"e_1_2_4_17_1","first-page":"35","article-title":"Pulmonary hypertension experience in an expert university hospital","volume":"20","author":"Sinan UY","year":"2018","journal-title":"Anatol J Cardiol."},{"key":"e_1_2_4_18_1","unstructured":"Compound Summary for CID 11304743.https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Riociguat. 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