{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T15:03:52Z","timestamp":1773155032577,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"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":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Macitentan has demonstrated its effectiveness in patients with pulmonary hypertension (PH), but its safety, especially for long\u2010term use, needs to be further explored. This systematic review and meta\u2010analysis aimed to determine the safety of long\u2010term use of macitentan in patients with PH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic search was made of PubMed, Embase, Cochrane Library and <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">clinicaltrials.gov<\/jats:ext-link>, without language restrictions. Randomised controlled trials (RCTs) on treatment of PH with macitentan, compared with placebo, were reviewed. Estimated effects of included studies were pooled as risk ratios (RRs), with 95% confidence intervals (CIs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Six RCTs (enrolling 1003 participants) met the inclusion criteria. Anaemia (RR 3.86, 95% CI 2.05\u20137.30), headache (RR 1.52, 95% CI 1.02\u20132.26) and bronchitis (RR 2.24, 95% CI 1.30\u20133.87) were more frequent in the macitentan groups. There was no statistically significant difference in the proportion of patients with at least one adverse event (AE) or serious adverse event (SAE), AEs leading to discontinuation of study treatment, all\u2010cause death, right ventricular failure (RVF) and peripheral oedema between the two groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The long\u2010term use of macitentan is safe for patients with PH, although with a higher risk of anaemia, headache and bronchitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.14059","type":"journal-article","created":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T07:34:10Z","timestamp":1688196850000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Long\u2010term safety of macitentan in patients with pulmonary hypertension: A meta\u2010analysis of randomised controlled trials"],"prefix":"10.1111","volume":"53","author":[{"given":"Guizuo","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Shaanxi Provincial People's Hospital Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinlv","family":"Qin","sequence":"additional","affiliation":[{"name":"Radioimmunoassay Center Shaanxi Provincial People's Hospital Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3775-4028","authenticated-orcid":false,"given":"Dong","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Shaanxi Provincial People's Hospital Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01913-2018"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpcardiol.2022.101466"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2020.04.039"},{"key":"e_1_2_10_5_1","volume-title":"Statpearls","author":"Pahal P","year":"2022"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2019.09.009"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047662"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm3009103"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(17)30305-3"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(19)30091-8"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1213917"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-151-4-200908180-00135"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2009.02234.x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0895-4356(92)90085-2"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2022.108986"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctim.2022.102907"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41440-022-00954-9"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/clc.23889"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2022.108960"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2022.06.014"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.2418"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.033575"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01886-2017"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(15)00543-3"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.003896"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2016.12.092"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.21037\/cdt.2019.03.02"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012212"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06250-X"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.04.050"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2001.114667"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2015.1000859"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.04.00028404"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1209657"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-151-4-200908180-00136"},{"key":"e_1_2_10_36_1","unstructured":"NCT02554903 trial.2021. 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