{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T17:40:07Z","timestamp":1789926007451,"version":"4.0.1"},"reference-count":121,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T00:00:00Z","timestamp":1684886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82200062"],"award-info":[{"award-number":["82200062"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22YF1439500"],"award-info":[{"award-number":["22YF1439500"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021-016"],"award-info":[{"award-number":["2021-016"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Yangfan Project of Science and Technology Commission of Shanghai Municipality","award":["82200062"],"award-info":[{"award-number":["82200062"]}]},{"name":"Yangfan Project of Science and Technology Commission of Shanghai Municipality","award":["22YF1439500"],"award-info":[{"award-number":["22YF1439500"]}]},{"name":"Yangfan Project of Science and Technology Commission of Shanghai Municipality","award":["2021-016"],"award-info":[{"award-number":["2021-016"]}]},{"name":"Youth Fund of Zhongshan Hospital, Fudan University","award":["82200062"],"award-info":[{"award-number":["82200062"]}]},{"name":"Youth Fund of Zhongshan Hospital, Fudan University","award":["22YF1439500"],"award-info":[{"award-number":["22YF1439500"]}]},{"name":"Youth Fund of Zhongshan Hospital, Fudan University","award":["2021-016"],"award-info":[{"award-number":["2021-016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular syndrome characterized by a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, which eventually leads to right heart failure and even death. Although the exact mechanism of PAH is not fully understood, pulmonary vasoconstriction, vascular remodeling, immune and inflammatory responses, and thrombosis are thought to be involved in the development and progression of PAH. In the era of non-targeted agents, PAH had a very dismal prognosis with a median survival time of only 2.8 years. With the deep understanding of the pathophysiological mechanism of PAH as well as advances in drug research, PAH-specific therapeutic drugs have developed rapidly in the past 30 years, but they primarily focus on the three classical signaling pathways, namely the endothelin pathway, nitric oxide pathway, and prostacyclin pathway. These drugs dramatically improved pulmonary hemodynamics, cardiac function, exercise tolerance, quality of life, and prognosis in PAH patients, but could only reduce pulmonary arterial pressure and right ventricular afterload to a limited extent. Current targeted agents delay the progression of PAH but cannot fundamentally reverse pulmonary vascular remodeling. Through unremitting efforts, new therapeutic drugs such as sotatercept have emerged, injecting new vitality into this field. This review comprehensively summarizes the general treatments for PAH, including inotropes and vasopressors, diuretics, anticoagulants, general vasodilators, and anemia management. Additionally, this review elaborates the pharmacological properties and recent research progress of twelve specific drugs targeting three classical signaling pathways, as well as dual-, sequential triple-, and initial triple-therapy strategies based on the aforementioned targeted agents. More crucially, the search for novel therapeutic targets for PAH has never stopped, with great progress in recent years, and this review outlines the potential PAH therapeutic agents currently in the exploratory stage to provide new directions for the treatment of PAH and improve the long-term prognosis of PAH patients.<\/jats:p>","DOI":"10.3390\/pharmaceutics15061579","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T01:29:26Z","timestamp":1684891766000},"page":"1579","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Medical Management of Pulmonary Arterial Hypertension: Current Approaches and Investigational Drugs"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3307-3663","authenticated-orcid":false,"given":"Qi","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, 180 Fenglin Road, Xuhui District, Shanghai 200032, China"},{"name":"National Clinical Research Center for Interventional Medicine, 180 Fenglin Road, Xuhui District, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, 180 Fenglin Road, Xuhui District, Shanghai 200032, China"},{"name":"National Clinical Research Center for Interventional Medicine, 180 Fenglin Road, Xuhui District, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, 180 Fenglin Road, Xuhui District, Shanghai 200032, China"},{"name":"National Clinical Research Center for Interventional Medicine, 180 Fenglin Road, Xuhui District, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai 201508, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongxiang","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai East Hospital, Shanghai Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, 180 Fenglin Road, Xuhui District, Shanghai 200032, China"},{"name":"National Clinical Research Center for Interventional Medicine, 180 Fenglin Road, Xuhui District, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, 180 Fenglin Road, Xuhui District, Shanghai 200032, China"},{"name":"National Clinical Research Center for Interventional Medicine, 180 Fenglin Road, Xuhui District, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhi","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, 180 Fenglin Road, Xuhui District, Shanghai 200032, China"},{"name":"National Clinical Research Center for Interventional Medicine, 180 Fenglin Road, Xuhui District, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daxin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, 180 Fenglin Road, Xuhui District, Shanghai 200032, China"},{"name":"National Clinical Research Center for Interventional Medicine, 180 Fenglin Road, Xuhui District, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbo","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, 180 Fenglin Road, Xuhui District, Shanghai 200032, China"},{"name":"National Clinical Research Center for Interventional Medicine, 180 Fenglin Road, Xuhui District, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1183\/13993003.01032-2015","article-title":"2015 ESC\/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT)","volume":"46","author":"Galie","year":"2015","journal-title":"Eur. 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