{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T18:36:59Z","timestamp":1772044619336,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":44,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pulm. circ."],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>This exploratory analysis assessed whether plasma biomarkers predict the response to switching from phosphodiesterase type 5 inhibitors (PDE5is) to the soluble guanylate cyclase stimulator riociguat in patients with pulmonary arterial hypertension. Selected biomarkers at baseline and their changes to Week 24 were evaluated in patients with and without a favorable response to riociguat in two trials: RESPITE, in which patients with an inadequate response to PDE5i were switched to riociguat; and REPLACE, in which patients at intermediate risk of 1\u2010year mortality despite a PDE5i were randomized to remain on PDE5i or were switched to riociguat. A response was defined as absence of clinical worsening and at least two of the following criteria: 6\u2010min walk distance increase by 10% or \u2265\u200930\u2009m, World Health Organization functional class I\/II, or <jats:italic>N<\/jats:italic>\u2010terminal prohormone of brain natriuretic peptide reduction of \u2265\u200930% at Week 24. In REPLACE, responders had significantly higher baseline cyclic guanosine monophosphate (cGMP) and significantly lower baseline asymmetric dimethylarginine, and growth\/differentiation factor 15 (GDF\u201015) than nonresponders. In RESPITE, responders had lower baseline GDF\u201015 than nonresponders, and nonresponders showed a significantly greater decrease in cGMP than responders. No baseline threshold value of any biomarker provided a good likelihood of predicting the response to riociguat. Overall, the biomarkers evaluated did not help to identify patients who were more likely to respond to switching from PDE5is to riociguat.<\/jats:p>","DOI":"10.1002\/pul2.70140","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T10:34:26Z","timestamp":1755167666000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Predicting Response to Switching From Phosphodiesterase Type 5 Inhibitor to Riociguat in Patients With Pulmonary Arterial Hypertension: Biomarker and Responder Analysis of the RESPITE and REPLACE Studies"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2997-5955","authenticated-orcid":false,"given":"James R.","family":"Klinger","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Sleep, and Critical Care Medicine, Rhode Island Hospital Alpert Medical School of Brown University Providence Rhode Island USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hikmet","family":"Al\u2010Hiti","sequence":"additional","affiliation":[{"name":"Department of Cardiology Institute of Clinical and Experimental Medicine\u2010IKEM Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5124-605X","authenticated-orcid":false,"given":"Sung\u2010A.","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Heart Vascular and Stroke Institute, Samsung Medical Center Sungkyunkwan University School of Medicine, Gangnam\u2010gu Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyuk J.","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Severance Cardiovascular Hospital, Yonsei University Health System Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hossein\u2010Ardeschir","family":"Ghofrani","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Justus\u2010Liebig\u2010University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC) Giessen Germany"},{"name":"Department of Pneumology Kerckhoff Heart and Thorax Center Bad Nauheim Germany"},{"name":"Department of Medicine Imperial College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekkehard","family":"Gr\u00fcnig","sequence":"additional","affiliation":[{"name":"Centre of Pulmonary Hypertension Thoraxklinik at Heidelberg University Hospital, Translational Lung Research Center (TLRC), member of DZL Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marius M.","family":"Hoeper","sequence":"additional","affiliation":[{"name":"Clinic for Respiratory Medicine, Hannover Medical School member of the German Centre for Lung Research (DZL) Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3711-7064","authenticated-orcid":false,"given":"Pavel","family":"Jansa","sequence":"additional","affiliation":[{"name":"Clinical Department of Cardiology and Angiology, First Faculty of Medicine, Second Medical Department Charles University Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5350-7679","authenticated-orcid":false,"given":"Jaquelina","family":"Ota\u2010Arakaki","sequence":"additional","affiliation":[{"name":"Pulmonary Circulation Group, Department of Medicine Universidade Federal de S\u00e3o Paulo\u2014Hospital S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomas","family":"Pulido","sequence":"additional","affiliation":[{"name":"Clinical Research Department National Heart Institute Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00e9rald","family":"Simonneau","sequence":"additional","affiliation":[{"name":"Assistance Publique\u2014H\u00f4pitaux de Paris, Service de Pneumologie, H\u00f4pital Bic\u00eatre Universit\u00e9 Paris\u2010Sud, Laboratoire d'Excellence en Recherche sur le M\u00e9dicament et Innovation Th\u00e9rapeutique, and Inserm U999 Le Kremlin\u2010Bic\u00eatre France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmine Dario","family":"Vizza","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Unit, Department of Cardiovascular and Respiratory Disease \u201cLa Sapienza\u201d University of Rome Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Rahner","sequence":"additional","affiliation":[{"name":"CHRESTOS Concept GmbH &amp; Co. 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