{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T21:45:10Z","timestamp":1765143910711,"version":"build-2065373602"},"reference-count":19,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T00:00:00Z","timestamp":1714089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health, Labor and Welfare of Japan","award":["20FC1027","23FC1031"],"award-info":[{"award-number":["20FC1027","23FC1031"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Pulmonary arterial hypertension (PAH) remains a significant challenge in cardiology, necessitating advancements in treatment strategies. This study explores the safety and efficacy of transitioning patients from beraprost to selexipag, a novel selective prostacyclin receptor agonist, within a Japanese cohort. Employing a multicenter, open-label, prospective design, 25 PAH patients inadequately managed on beraprost were switched to selexipag. Key inclusion criteria included ongoing beraprost therapy for \u22653 months, a diagnosis of PAH confirmed by mean pulmonary artery pressure (mPAP) \u2265 25 mmHg, and current treatment with endothelin receptor antagonists and\/or phosphodiesterase type 5 inhibitors. Outcomes assessed were changes in hemodynamic parameters (mPAP, cardiac index, pulmonary vascular resistance) and the 6 min walk distance (6-MWD) over 3\u20136 months. The study found no statistically significant changes in these parameters post-switch. However, a subset of patients, defined as responders, demonstrated improvements in all measured hemodynamic parameters, suggesting a potential benefit in carefully selected patients. The transition was generally well-tolerated with no serious adverse events reported. This investigation underscores the importance of personalized treatment strategies in PAH, highlighting that certain patients may benefit from switching to selexipag, particularly those previously on higher doses of beraprost. Further research is needed to elucidate the predictors of positive response to selexipag and optimize treatment regimens for this complex condition.<\/jats:p>","DOI":"10.3390\/ph17050555","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T08:18:27Z","timestamp":1714119507000},"page":"555","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Switching from Beraprost to Selexipag in the Treatment of Pulmonary Arterial Hypertension: Insights from a Phase IV Study of the Japanese Registry (The EXCEL Study: EXChange from bEraprost to seLexipag Study)"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4437-8019","authenticated-orcid":false,"given":"Yuichi","family":"Tamura","sequence":"first","affiliation":[{"name":"Pulmonary Hypertension Center, International University of Health and Welfare Mita Hospital, Tokyo 108-8329, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiraku","family":"Kumamaru","sequence":"additional","affiliation":[{"name":"Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8654, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0196-9572","authenticated-orcid":false,"given":"Ichizo","family":"Tsujino","sequence":"additional","affiliation":[{"name":"Division of Respiratory and Cardiovascular Innovative Research, Faculty of Medicine, Hokkaido University, Sapporo 060-8638, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rika","family":"Suda","sequence":"additional","affiliation":[{"name":"Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kohtaro","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takumi","family":"Inami","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyorin University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koshin","family":"Horimoto","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Matsuyama Red Cross Hospital, Matsuyama 790-0826, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiro","family":"Adachi","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Nagoya University Hospital, Nagoya 466-8560, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-0872, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fusako","family":"Sera","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8352-6136","authenticated-orcid":false,"given":"Masataka","family":"Kuwana","sequence":"additional","affiliation":[{"name":"Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo 113-8602, Japan"},{"name":"Scleroderma\/Myositis Center of Excellence (SMCE), Nippon Medical School Hospital, Tokyo 113-8603, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichiro","family":"Tatsumi","sequence":"additional","affiliation":[{"name":"Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,26]]},"reference":[{"key":"ref_1","first-page":"1801887","article-title":"Pathology and Pathobiology of Pulmonary Hypertension: State of the Art and Research Perspectives","volume":"53","author":"Humbert","year":"2019","journal-title":"Eur. Respir. J. Off. J. Eur. Soc. Clin. Respir. Physiol."},{"key":"ref_2","first-page":"1801889","article-title":"Risk Stratification and Medical Therapy of Pulmonary Arterial Hypertension","volume":"53","author":"Channick","year":"2019","journal-title":"Eur. Respir. J. Off. J. Eur. Soc. Clin. Respir. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.jacasi.2022.02.011","article-title":"Changes in the Characteristics and Initial Treatments of Pulmonary Hypertension between 2008 and 2020 in Japan","volume":"2","author":"Tamura","year":"2022","journal-title":"JACC Asia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1536\/ihj.23-047","article-title":"Initial Triple Combination Therapy Including Intravenous Prostaglandin I2 for the Treatment of Patients with Severe Pulmonary Arterial Hypertension","volume":"64","author":"Tamura","year":"2023","journal-title":"Int. Heart J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1161\/CIRCULATIONAHA.114.006974","article-title":"Advances in therapeutic interventions for patients with pulmonary arterial hypertension","volume":"130","author":"Humbert","year":"2014","journal-title":"Circulation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.phrs.2011.03.003","article-title":"The role of endothelin-1 in the pathogenesis of pulmonary arterial hypertension","volume":"63","author":"Shao","year":"2011","journal-title":"Pharmacol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1136\/thoraxjnl-2015-207170","article-title":"The molecular targets of approved treatments for pulmonary arterial hypertension","volume":"71","author":"Humbert","year":"2016","journal-title":"Thorax"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1056\/NEJMoa012212","article-title":"Bosentan therapy for pulmonary arterial hypertension","volume":"346","author":"Rubin","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1161\/CIRCULATIONAHA.107.742510","article-title":"Ambrisentan for the treatment of pulmonary arterial hypertension: Results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2","volume":"117","author":"Olschewski","year":"2008","journal-title":"Circulation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1056\/NEJMoa1213917","article-title":"Macitentan and morbidity and mortality in pulmonary arterial hypertension","volume":"369","author":"Pulido","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9442","DOI":"10.1002\/anie.201302588","article-title":"The chemistry and biology of soluble guanylate cyclase stimulators and activators","volume":"52","author":"Follmann","year":"2013","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1164\/rccm.201304-0686PP","article-title":"Nitric oxide deficiency and endothelial dysfunction in pulmonary arterial hypertension","volume":"188","author":"Klinger","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1056\/NEJMoa1209655","article-title":"Riociguat for the treatment of pulmonary arterial hypertension","volume":"369","author":"Ghofrani","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1016\/S0735-1097(99)00312-5","article-title":"Effect of Orally Active Prostacyclin Analogue on Survival of Outpatients with Primary Pulmonary Hypertension","volume":"34","author":"Nagaya","year":"1999","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1016\/S0735-1097(03)00463-7","article-title":"Beraprost Therapy for Pulmonary Arterial Hypertension","volume":"41","author":"Barst","year":"2003","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.1056\/NEJMoa1503184","article-title":"Selexipag for the Treatment of Pulmonary Arterial Hypertension","volume":"373","author":"Sitbon","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1017\/S1047951122000415","article-title":"Clinical Efficacy and Safety of Selexipag in Children and Young Adults with Idiopathic and Heritable Pulmonary Arterial Hypertension","volume":"33","author":"Takatsuki","year":"2023","journal-title":"Cardiol. Young"},{"key":"ref_18","first-page":"1360","article-title":"Efficacy and Safety of an Orally Administered Selective Prostacyclin Receptor Agonist, Selexipag, in Japanese Patients with Pulmonary Arterial Hypertension","volume":"81","author":"Tanabe","year":"2017","journal-title":"Circ. J. Off. J. Jpn. Circ. Soc."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tamura, Y., Kumamaru, H., Abe, K., Satoh, T., Miyata, H., Ogawa, A., Tanabe, N., Hatano, M., Yao, A., and Tsujino, I. (2021). Improvements in French Risk Stratification Score Were Correlated with Reductions in Mean Pulmonary Artery Pressure in Pulmonary Arterial Hypertension: A Subanalysis of the Japan Pulmonary Hypertension Registry (JAPHR). BMC Pulm. Med., 21.","DOI":"10.1186\/s12890-021-01398-6"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/5\/555\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:33:28Z","timestamp":1760106808000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/5\/555"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,26]]},"references-count":19,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["ph17050555"],"URL":"https:\/\/doi.org\/10.3390\/ph17050555","relation":{},"ISSN":["1424-8247"],"issn-type":[{"type":"electronic","value":"1424-8247"}],"subject":[],"published":{"date-parts":[[2024,4,26]]}}}