{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:33:47Z","timestamp":1786977227230,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870254"],"award-info":[{"award-number":["81870254"]}],"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":["2019B020230004"],"award-info":[{"award-number":["2019B020230004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Innovation"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>With the emergence of cytotoxic T lymphocyte\u2010associated protein\u20104 (CTLA\u20104) inhibitors, the outcomes of patients with malignant tumors have improved significantly. However, the incidence of cardiovascular adverse events has also increased, which can affect tumor treatment. In this study, we evaluated the incidence and severity of adverse cardiovascular events caused by CTLA\u20104 inhibitors by analyzing reported trials that involved CTLA\u20104 inhibitor therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Randomized clinical trials published in English from January 1, 2013, to November 30, 2022, were searched using the Cochrane Library and PubMed databases. All included trials examined all grade and grades 3\u20135 cardiac and vascular adverse events. These involved comparisons of CTLA\u20104 inhibitors to placebo, CTLA\u20104 inhibitors plus chemotherapy to chemotherapy alone, CTLA\u20104 inhibitors combined with PD\u20101\/PD\u2010L1 inhibitors to PD\u20101\/PD\u2010L1 inhibitors alone, and CTLA\u20104 inhibitors plus target agent to PD\u20101\/PD\u2010L1 inhibitors plus target agent. The odds ratio (OR) and corresponding 95% confidence intervals (CIs) were calculated using the Mantel\u2010Haenszel method.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall, 20 trials were included. CTLA\u20104 inhibitors significantly increased the incidence of all\u2010grade cardiovascular toxicity (OR\u2009=\u20091.33, 95% CI: 1.00\u20131.75,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.05). The incidence of all\u2010grade cardiovascular toxicity increased in malignant tumor patients who received single\u2010agent CTLA\u20104 inhibitors (OR\u2009=\u20091.73, 95% CI: 1.13\u20132.65,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01), as well as the incidence rate of grades 3\u20135 cardiovascular adverse events (OR\u2009=\u20092.00, 95% CI: 1.08\u20133.70,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03). Compared with the non\u2010CTLA\u20104 inhibitor group, CTLA\u20104 inhibitors plus chemotherapy, PD\u20101\/PD\u2010L1 inhibitors, or target agent did not significantly affect the incidence of cardiac and vascular toxicity. The incidence of grades 3\u20135 cardiac failure, hypertension, pericardial effusion, myocarditis, and atrial fibrillation were much higher among patients exposed to CTLA\u20104 inhibitor, but the data were not statistically significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest that the incidence rate of all cardiovascular toxicity and severe cardiovascular toxicity increased in patients who were administered CTLA\u20104 inhibitors. In addition, the risk of serious cardiovascular toxic events was independent of the type of adverse event. From these results, physicians should assess the benefits and risks of CTLA\u20104 inhibitors when treating malignancies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cai2.116","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T04:05:25Z","timestamp":1713240325000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cardiovascular toxicity with CTLA\u20104 inhibitors in cancer patients: A meta\u2010analysis"],"prefix":"10.1002","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5806-1023","authenticated-orcid":false,"given":"Huiyi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyu","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"},{"name":"The Second School of Clinical Medicine Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingdong","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijia","family":"Pu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"},{"name":"School of Medicine South China University of Technology  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumei","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"},{"name":"Guangdong Provincial Key Laboratory of Clinical Pharmacology, Research Center of Medical Sciences, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1840703"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23086"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvz026"},{"key":"e_1_2_13_4_2","doi-asserted-by":"crossref","unstructured":"Erratum in: Cardiovasc Res.2019;115(5):868","DOI":"10.1093\/cvr\/cvz082"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2006.01.011"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt161"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2017.09.030"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(18)30765-4"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(22)00369-2"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.02.022"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213-2600(18)30151-6"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000133187.74800.B9"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(16)30098-5"},{"key":"e_1_2_13_13_2","doi-asserted-by":"crossref","unstructured":"Erratum in: Lancet Oncol.2016;17(7):e270.","DOI":"10.1016\/S1470-2045(16)30246-7"},{"key":"e_1_2_13_13_3","doi-asserted-by":"crossref","unstructured":"Erratum in: Lancet Oncol.2019;20(2):e70.","DOI":"10.1016\/S1470-2045(19)30018-X"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2016.69.1584"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.20.03579"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-01224-2"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.4593"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1611299"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(20)30539-8"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(18)30700-9"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(14)70189-5"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(17)30446-1"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2022.100408"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.02.006"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(20)30541-6"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2012.44.6112"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04508-4"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.19.01381"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-20-0328"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(20)30417-7"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-11-1595"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0218-0"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.2289"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2022.101383"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-015-0455-8"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.cji.0000208259.73167.58"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-07-0187"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2005.06.205"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmc1901677"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2021.102282"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.117.029626"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm955"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-021-01070-6"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1504030"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1712126"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(17)30422-9"},{"key":"e_1_2_13_46_2","doi-asserted-by":"crossref","unstructured":"Erratum in: Lancet Oncol.2017;18(9):e510.","DOI":"10.1016\/S1470-2045(17)30591-0"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k4226"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.908173"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt-2018-0118"}],"container-title":["Cancer Innovation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cai2.116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T01:33:27Z","timestamp":1715218407000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cai2.116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,16]]},"references-count":52,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/cai2.116"],"URL":"https:\/\/doi.org\/10.1002\/cai2.116","archive":["Portico"],"relation":{},"ISSN":["2770-9191","2770-9183"],"issn-type":[{"value":"2770-9191","type":"print"},{"value":"2770-9183","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,16]]},"assertion":[{"value":"2023-10-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e116"}}