{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:01:06Z","timestamp":1792008066560,"version":"4.4.0"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2016,10,26]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Evidence of the clinical safety of endothelin receptor antagonists (ERAs) is limited and derived mainly from individual trials; therefore, we conducted a meta\u2010analysis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              After systematic searches of the Medline, Embase, and Cochrane Library databases and the\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n              website, randomized controlled trials with patients receiving ERAs (bosentan, macitentan, or ambrisentan) in at least 1 treatment group were included. All reported adverse events of ERAs were evaluated. Summary relative risks and 95% CIs were calculated using random\u2010 or fixed\u2010effects models according to between\u2010study heterogeneity. In total, 24 randomized trials including 4894 patients met the inclusion criteria. Meta\u2010analysis showed that the incidence of abnormal liver function (7.91% versus 2.84%; risk ratio [RR] 2.38, 95% CI 1.36\u20134.18), peripheral edema (14.36% versus 9.68%; RR 1.44, 95% CI 1.20\u20131.74), and anemia (6.23% versus 2.44%; RR 2.69, 95% CI 1.78\u20134.07) was significantly higher in the ERA group compared with placebo. In comparisons of individual ERAs with placebo, bosentan (RR 3.78, 95% CI 2.42\u20135.91) but not macitentan (RR 1.17, 95% CI 0.42\u20133.31) significantly increased the risk of abnormal liver function, whereas ambrisentan (RR 0.06, 95% CI 0.01\u20130.45) significantly decreased that risk. Bosentan (RR 1.47, 95% CI 1.06\u20132.03) and ambrisentan (RR 2.02, 95% CI 1.40\u20132.91) but not macitentan (RR 1.08, 95% CI 0.81\u20131.46) significantly increased the risk of peripheral edema. Bosentan (RR 3.09, 95% CI 1.52\u20136.30) and macitentan (RR 2.63, 95% CI 1.54\u20134.47) but not ambrisentan (RR 1.30, 95% CI 0.20\u20138.48) significantly increased the risk of anemia. ERAs were not found to increase other reported adverse events compared with placebo.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">The present meta\u2010analysis showed that the main adverse effects of treatment with ERAs were hepatic transaminitis (bosentan), peripheral edema (bosentan and ambrisentan), and anemia (bosentan and macitentan).<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.116.003896","type":"journal-article","created":{"date-parts":[[2016,10,27]],"date-time":"2016-10-27T02:40:19Z","timestamp":1477536019000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":120,"title":["Clinical Adverse Effects of Endothelin Receptor Antagonists: Insights From the Meta\u2010Analysis of 4894 Patients From 24 Randomized Double\u2010Blind Placebo\u2010Controlled Clinical Trials"],"prefix":"10.1161","volume":"5","author":[{"given":"Anhua","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhichun","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, RenJi Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"},{"name":"School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, RenJi Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Han","sequence":"additional","affiliation":[{"name":"Geriatric ICU, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Pu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, RenJi Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccl.2016.04.006"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12263"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12184"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.742510"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012212"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.04.00028404"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200307-957OC"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.01.057"},{"key":"e_1_3_5_10_2","unstructured":"Formulary Journal . 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