{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:25:56Z","timestamp":1791645956603,"version":"4.3.4"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T00:00:00Z","timestamp":1660694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012476","name":"Fundamental Research Funds for Central Universities of the Central South University","doi-asserted-by":"publisher","award":["2021zzts0388"],"award-info":[{"award-number":["2021zzts0388"]}],"id":[{"id":"10.13039\/501100012476","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012476","name":"Fundamental Research Funds for Central Universities of the Central South University","doi-asserted-by":"publisher","award":["2021zzts1054"],"award-info":[{"award-number":["2021zzts1054"]}],"id":[{"id":"10.13039\/501100012476","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pulmonary Pharmacology &amp; Therapeutics"],"published-print":{"date-parts":[[2022,10]]},"DOI":"10.1016\/j.pupt.2022.102144","type":"journal-article","created":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T21:01:59Z","timestamp":1659214919000},"page":"102144","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":8,"special_numbering":"C","title":["Efficacy and safety of sequential combination therapy for pulmonary arterial hypertension: A meta-analysis of Randomized-Controlled Trials"],"prefix":"10.1016","volume":"76","author":[{"given":"Zhen","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan-yun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng-teng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9125-5348","authenticated-orcid":false,"given":"Zhen-fei","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.pupt.2022.102144_bib1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/eurheartj\/ehv317","volume":"37","author":"Galie","year":"2016","journal-title":"Eur. Heart J."},{"key":"10.1016\/j.pupt.2022.102144_bib2","doi-asserted-by":"crossref","first-page":"j5492","DOI":"10.1136\/bmj.j5492","article-title":"Pulmonary arterial hypertension: pathogenesis and clinical management","volume":"360","author":"Thenappan","year":"2018","journal-title":"BMJ"},{"issue":"4","key":"10.1016\/j.pupt.2022.102144_bib3","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."},{"issue":"4","key":"10.1016\/j.pupt.2022.102144_bib4","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1183\/09031936.00137511","article-title":"Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension","volume":"40","author":"Simonneau","year":"2012","journal-title":"Eur. Respir. J."},{"issue":"1 Suppl","key":"10.1016\/j.pupt.2022.102144_bib5","doi-asserted-by":"crossref","first-page":"S78","DOI":"10.1016\/j.jacc.2009.04.017","article-title":"Updated evidence-based treatment algorithm in pulmonary arterial hypertension","volume":"54","author":"Barst","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"issue":"2","key":"10.1016\/j.pupt.2022.102144_bib6","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.ahj.2009.11.028","article-title":"Systematic review of trials using vasodilators in pulmonary arterial hypertension: why a new approach is needed","volume":"159","author":"Macchia","year":"2010","journal-title":"Am. Heart J."},{"issue":"2","key":"10.1016\/j.pupt.2022.102144_bib7","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.chest.2016.03.031","article-title":"Efficacy and safety of pulmonary arterial hypertension-specific therapy in pulmonary arterial hypertension: a meta-analysis of randomized controlled trials","volume":"150","author":"Liu","year":"2016","journal-title":"Chest"},{"issue":"20","key":"10.1016\/j.pupt.2022.102144_bib8","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1093\/eurheartj\/ehp297","volume":"30","author":"Galie","year":"2009","journal-title":"Eur. Heart J."},{"issue":"2","key":"10.1016\/j.pupt.2022.102144_bib9","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1378\/chest.14-0793","article-title":"Pharmacologic therapy for pulmonary arterial hypertension in adults: CHEST guideline and expert panel report","volume":"146","author":"Taichman","year":"2014","journal-title":"Chest"},{"issue":"3","key":"10.1016\/j.pupt.2022.102144_bib10","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.chest.2018.11.030","article-title":"Therapy for pulmonary arterial hypertension in adults: update of the CHEST guideline and expert panel report","volume":"155","author":"Klinger","year":"2019","journal-title":"Chest"},{"issue":"3","key":"10.1016\/j.pupt.2022.102144_bib11","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1378\/chest.12-2875","article-title":"Oral treprostinil for the treatment of pulmonary arterial hypertension in patients receiving background endothelin receptor antagonist and phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C2 study): a randomized controlled trial","volume":"144","author":"Tapson","year":"2013","journal-title":"Chest"},{"issue":"17","key":"10.1016\/j.pupt.2022.102144_bib12","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1093\/eurheartj\/ehq152","article-title":"Pulmonary arterial hypertension: from the kingdom of the near-dead to multiple clinical trial meta-analyses","volume":"31","author":"Galie","year":"2010","journal-title":"Eur. Heart J."},{"issue":"3","key":"10.1016\/j.pupt.2022.102144_bib13","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1159\/000334431","article-title":"Combination therapy in pulmonary arterial hypertension: a meta-analysis","volume":"120","author":"Bai","year":"2011","journal-title":"Cardiology"},{"key":"10.1016\/j.pupt.2022.102144_bib14","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.rmed.2017.03.025","article-title":"Clinical and hemodynamic improvements after adding ambrisentan to background PDE5i therapy in patients with pulmonary arterial hypertension exhibiting a suboptimal therapeutic response (ATHENA-1)","volume":"126","author":"Shapiro","year":"2017","journal-title":"Respir. Med."},{"issue":"5","key":"10.1016\/j.pupt.2022.102144_bib15","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1183\/09031936.00105914","article-title":"Patent plus: a blinded, randomised and extension study of riociguat plus sildenafil in pulmonary arterial hypertension","volume":"45","author":"Galie","year":"2015","journal-title":"Eur. Respir. J."},{"issue":"2","key":"10.1016\/j.pupt.2022.102144_bib16","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1183\/13993003.02044-2014","article-title":"Bosentan added to sildenafil therapy in patients with pulmonary arterial hypertension","volume":"46","author":"McLaughlin","year":"2015","journal-title":"Eur. Respir. J."},{"issue":"1","key":"10.1016\/j.pupt.2022.102144_bib17","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3899\/jrheum.180595","article-title":"Longterm efficacy and safety of monotherapy versus combination therapy in systemic sclerosis-associated pulmonary arterial hypertension: a retrospective RESCLE registry study","volume":"47","author":"Pestana-Fernandez","year":"2020","journal-title":"J. Rheumatol."},{"issue":"8","key":"10.1016\/j.pupt.2022.102144_bib18","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/j.amjcard.2011.06.021","article-title":"Meta-analysis of monotherapy versus combination therapy for pulmonary arterial hypertension","volume":"108","author":"Fox","year":"2011","journal-title":"Am. J. Cardiol."},{"issue":"4","key":"10.1016\/j.pupt.2022.102144_bib19","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S2213-2600(16)00027-8","article-title":"Combination therapy versus monotherapy for pulmonary arterial hypertension: a meta-analysis","volume":"4","author":"Lajoie","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"10.1016\/j.pupt.2022.102144_bib20","doi-asserted-by":"crossref","first-page":"b2535","DOI":"10.1136\/bmj.b2535","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement","volume":"339","author":"Moher","year":"2009","journal-title":"BMJ"},{"issue":"1","key":"10.1016\/j.pupt.2022.102144_bib21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0197-2456(95)00134-4","article-title":"Assessing the quality of reports of randomized clinical trials: is blinding necessary?","volume":"17","author":"Jadad","year":"1996","journal-title":"Contr. Clin. Trials"},{"key":"10.1016\/j.pupt.2022.102144_bib22","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1471-2288-5-13","article-title":"Estimating the mean and variance from the median, range, and the size of a sample","volume":"5","author":"Hozo","year":"2005","journal-title":"BMC Med. Res. Methodol."},{"issue":"4","key":"10.1016\/j.pupt.2022.102144_bib23","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.2307\/2533446","article-title":"Operating characteristics of a rank correlation test for publication bias","volume":"50","author":"Begg","year":"1994","journal-title":"Biometrics"},{"issue":"4","key":"10.1016\/j.pupt.2022.102144_bib24","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1183\/09031936.06.00057906","article-title":"Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary arterial hypertension","volume":"28","author":"Hoeper","year":"2006","journal-title":"Eur. Respir. J."},{"issue":"11","key":"10.1016\/j.pupt.2022.102144_bib25","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1164\/rccm.200603-358OC","article-title":"Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension","volume":"174","author":"McLaughlin","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."},{"issue":"8","key":"10.1016\/j.pupt.2022.102144_bib26","doi-asserted-by":"crossref","first-page":"521","DOI":"10.7326\/0003-4819-149-8-200810210-00004","article-title":"Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial","volume":"149","author":"Simonneau","year":"2008","journal-title":"Ann. Intern. Med."},{"issue":"18","key":"10.1016\/j.pupt.2022.102144_bib27","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1016\/j.jacc.2010.01.027","article-title":"Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial","volume":"55","author":"McLaughlin","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"issue":"9","key":"10.1016\/j.pupt.2022.102144_bib28","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1093\/eurheartj\/ehq011","article-title":"Combination therapy with bosentan and sildenafil in Eisenmenger syndrome: a randomized, placebo-controlled, double-blinded trial","volume":"31","author":"Iversen","year":"2010","journal-title":"Eur. Heart J."},{"issue":"6","key":"10.1016\/j.pupt.2022.102144_bib29","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.healun.2010.11.009","article-title":"Tadalafil monotherapy and as add-on to background bosentan in patients with pulmonary arterial hypertension","volume":"30","author":"Barst","year":"2011","journal-title":"J. Heart Lung Transplant."},{"issue":"6","key":"10.1016\/j.pupt.2022.102144_bib30","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1378\/chest.11-2212","article-title":"Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and\/or phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C study): a randomized controlled trial","volume":"142","author":"Tapson","year":"2012","journal-title":"Chest"},{"issue":"6","key":"10.1016\/j.pupt.2022.102144_bib31","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/hr.2014.28","article-title":"Randomized study of adding tadalafil to existing ambrisentan in pulmonary arterial hypertension","volume":"37","author":"Zhuang","year":"2014","journal-title":"Hypertens. Res."},{"issue":"3","key":"10.1016\/j.pupt.2022.102144_bib32","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.healun.2014.12.001","article-title":"Use of clinically relevant responder threshold criteria to evaluate the response to treatment in the phase III PATENT-1 study","volume":"34","author":"Langleben","year":"2015","journal-title":"J. Heart Lung Transplant."},{"issue":"26","key":"10.1016\/j.pupt.2022.102144_bib33","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."},{"issue":"1","key":"10.1016\/j.pupt.2022.102144_bib34","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1186\/s12872-017-0674-3","article-title":"Sildenafil dosed concomitantly with bosentan for adult pulmonary arterial hypertension in a randomized controlled trial","volume":"17","author":"Vizza","year":"2017","journal-title":"BMC Cardiovasc. Disord."},{"issue":"6","key":"10.1016\/j.pupt.2022.102144_bib35","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1164\/rccm.201908-1640OC","article-title":"Combination therapy with oral treprostinil for pulmonary arterial hypertension. a double-blind placebo-controlled clinical trial","volume":"201","author":"White","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"issue":"1","key":"10.1016\/j.pupt.2022.102144_bib36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40256-017-0260-1","article-title":"Macitentan in pulmonary arterial hypertension: a focus on combination therapy in the SERAPHIN trial","volume":"18","author":"Jansa","year":"2018","journal-title":"Am. J. Cardiovasc. Drugs"},{"issue":"9","key":"10.1016\/j.pupt.2022.102144_bib37","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."},{"issue":"4","key":"10.1016\/j.pupt.2022.102144_bib38","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/S0735-1097(02)02012-0","article-title":"Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival","volume":"40","author":"Sitbon","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"issue":"12","key":"10.1016\/j.pupt.2022.102144_bib39","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1161\/01.CIR.0000029100.82385.58","article-title":"Survival in primary pulmonary hypertension: the impact of epoprostenol therapy","volume":"106","author":"McLaughlin","year":"2002","journal-title":"Circulation"},{"issue":"12","key":"10.1016\/j.pupt.2022.102144_bib40","first-page":"1520","article-title":"Combination therapy for pulmonary arterial hypertension: a systematic review and meta-analysis","volume":"32","author":"Fox","year":"2016","journal-title":"Can. J. Cardiol."},{"key":"10.1016\/j.pupt.2022.102144_bib41","doi-asserted-by":"crossref","first-page":"515","DOI":"10.7326\/0003-4819-136-7-200204020-00008","article-title":"Combination therapy with oral sildenafifil and inhaled iloprost for severe pulmonary hypertension","volume":"136","author":"Ghofrani","year":"2002","journal-title":"Ann. Intern. Med."},{"issue":"3","key":"10.1016\/j.pupt.2022.102144_bib42","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1183\/09031936.00092311","article-title":"The prognostic impact of follow-up assessments in patients with idiopathic pulmonary arterial hypertension","volume":"39","author":"Nickel","year":"2012","journal-title":"Eur. Respir. J."},{"issue":"1","key":"10.1016\/j.pupt.2022.102144_bib43","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1378\/chest.12-2417","article-title":"Functional class improvement and 3-year survival outcomes in patients with pulmonary arterial hypertension in the REVEAL Registry","volume":"144","author":"Barst","year":"2013","journal-title":"Chest"},{"issue":"3","key":"10.1016\/j.pupt.2022.102144_bib44","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.healun.2014.08.020","article-title":"Predicting outcomes in pulmonary arterial hypertension based on the 6-minute walk distance","volume":"34","author":"Farber","year":"2015","journal-title":"J. Heart Lung Transplant."},{"issue":"1","key":"10.1016\/j.pupt.2022.102144_bib45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jchf.2014.07.013","article-title":"Effect of macitentan on hospitalizations: results from the SERAPHIN trial","volume":"3","author":"Channick","year":"2015","journal-title":"JACC Heart Fail"},{"issue":"5","key":"10.1016\/j.pupt.2022.102144_bib46","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1378\/chest.13-1864","article-title":"Comparative effectiveness and safety of drug therapy for pulmonary arterial hypertension: a systematic review and meta-analysis","volume":"145","author":"Coeytaux","year":"2014","journal-title":"Chest"},{"issue":"25 Suppl","key":"10.1016\/j.pupt.2022.102144_bib47","doi-asserted-by":"crossref","first-page":"D60","DOI":"10.1016\/j.jacc.2013.10.031","article-title":"Updated treatment algorithm of pulmonary arterial hypertension","volume":"62","author":"Gali\u00e8","year":"2013","journal-title":"J. Am. Coll. Cardiol."}],"container-title":["Pulmonary Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1094553922000359?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1094553922000359?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T21:31:01Z","timestamp":1761082261000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1094553922000359"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10]]},"references-count":47,"alternative-id":["S1094553922000359"],"URL":"https:\/\/doi.org\/10.1016\/j.pupt.2022.102144","relation":{},"ISSN":["1094-5539"],"issn-type":[{"value":"1094-5539","type":"print"}],"subject":[],"published":{"date-parts":[[2022,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Efficacy and safety of sequential combination therapy for pulmonary arterial hypertension: A meta-analysis of Randomized-Controlled Trials","name":"articletitle","label":"Article Title"},{"value":"Pulmonary Pharmacology & Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.pupt.2022.102144","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"102144"}}