{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T10:54:05Z","timestamp":1793357645680,"version":"4.5.0"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":22,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Society of Clinical Epidemiology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Large, diverse cohort studies are essential for determining the incidence and risk factors of major adverse cardiovascular events (MACEs) associated with immune checkpoint inhibitors (ICIs). This study aimed to (1) compare the incidence of MACEs in primary lung cancer patients receiving ICIs versus those receiving non-ICI chemotherapy, and (2) identify risk factors for MACEs in ICI-treated patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and methods<\/jats:title>\n                  <jats:p>We performed a retrospective analysis of primary lung cancer patients using a nationwide Japanese database. Patients were stratified by their use of ICIs, and after propensity score matching, outcomes were evaluated over 180 days.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The study included 743 propensity-matched patients in each cohort. The median follow-up period was 329 days (interquartile range, 147-625). At 180 days, 4.0% of ICI-treated patients experienced MACEs, significantly higher than those treated with non-ICI chemotherapy (hazard ratio [HR], 1.98; 95% confidence interval [CI], 1.07-3.69; P-value\u2005=\u2005.030). Among MACEs, myocarditis and pericarditis occurred significantly more frequently in patients receiving ICI treatment than in those receiving non-ICI chemotherapy (P-value\u2005=\u2005.048 for both outcomes). No significant differences were observed in other MACE components. In multivariable analysis, chronic renal failure (HR, 2.16; 95% CI, 1.05-4.46; P-value\u2005=\u20050.038) and prior heart failure (HR, 3.08; 95% CI, 1.86-5.11; P-value\u2005&amp;lt;\u20050.001) were significant risk factors for MACEs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>ICI treatment was associated with more frequent MACEs, primarily due to myocarditis and pericarditis. Additionally, prior heart failure and chronic renal failure were key risk factors for MACEs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical trial registration<\/jats:title>\n                  <jats:p>UMIN000051698<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyaf151","type":"journal-article","created":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T01:09:27Z","timestamp":1751159367000},"source":"Crossref","is-referenced-by-count":2,"title":["Cardiovascular adverse events in patients with lung cancer treated with immune checkpoint inhibitors: a nationwide database study"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1271-0344","authenticated-orcid":false,"given":"Tsuyoshi","family":"Isawa","sequence":"first","affiliation":[{"name":"Department of Cardiology, Sendai Kousei Hospital , Sendai 981-0914 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shintaro","family":"Togashi","sequence":"additional","affiliation":[{"name":"Department of Nursing Care, Sendai Kousei Hospital , Sendai 981-0914 ,","place":["Japan"]},{"name":"Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health , Wako 351-0197 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masataka","family":"Taguri","sequence":"additional","affiliation":[{"name":"Department of Health Data Science, Tokyo Medical University , Tokyo 160-8402 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5983-3531","authenticated-orcid":false,"given":"Yukihiro","family":"Toi","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Sendai Kousei Hospital , Sendai 981-0914 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3427-4558","authenticated-orcid":false,"given":"Shunichi","family":"Sugawara","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Sendai Kousei Hospital , Sendai 981-0914 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Toyoda","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Dokkyo Medical University , Mibu 321-0293 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,6,23]]},"reference":[{"key":"2025062821092272400_CIT0001","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1001\/jamaoncol.2018.3923","article-title":"Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis","volume":"4","author":"Wang","year":"2018","journal-title":"JAMA Oncol"},{"key":"2025062821092272400_CIT0002","doi-asserted-by":"publisher","first-page":"4073","DOI":"10.1200\/JCO.21.01440","article-title":"Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update","volume":"39","author":"Schneider","year":"2021","journal-title":"J Clin Oncol"},{"key":"2025062821092272400_CIT0003","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/j.cjca.2019.11.035","article-title":"Acute coronary syndrome with immune checkpoint inhibitors: a proof-of-concept case and pharmacovigilance analysis of a life-threatening adverse event","volume":"36","author":"Cautela","year":"2020","journal-title":"Can J Cardiol"},{"key":"2025062821092272400_CIT0004","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1093\/jjco\/hyac150","article-title":"The incidence and risk of cardiovascular events associated with immune checkpoint inhibitors in Asian populations","volume":"52","author":"Chiang","year":"2022","journal-title":"Jpn J Clin Oncol"},{"key":"2025062821092272400_CIT0005","doi-asserted-by":"publisher","first-page":"e410","DOI":"10.1093\/oncolo\/oyac056","article-title":"Incidence, clinical characteristics, and predictors of cardiovascular immune-related adverse events associated with immune checkpoint inhibitors","volume":"27","author":"Isawa","year":"2022","journal-title":"Oncologist"},{"key":"2025062821092272400_CIT0006","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.jaccao.2019.11.013","article-title":"Immune checkpoint inhibitor-related adverse cardiovascular events in patients with lung cancer","volume":"1","author":"Chitturi","year":"2019","journal-title":"JACC CardioOncol"},{"key":"2025062821092272400_CIT0007","doi-asserted-by":"publisher","first-page":"3439","DOI":"10.1200\/JCO.22.00369","article-title":"Major adverse cardiac events with immune checkpoint inhibitors: a pooled analysis of trials sponsored by the National Cancer Institute-Cancer Therapy Evaluation Program","volume":"40","author":"Naqash","year":"2022","journal-title":"J Clin Oncol"},{"key":"2025062821092272400_CIT0008","doi-asserted-by":"publisher","first-page":"2594","DOI":"10.1161\/CIRCULATIONAHA.118.039180","article-title":"Representation of patients with cardiovascular disease in pivotal cancer clinical trials","volume":"139","author":"Bonsu","year":"2019","journal-title":"Circulation"},{"key":"2025062821092272400_CIT0009","doi-asserted-by":"publisher","first-page":"3172","DOI":"10.1002\/cam4.5171","article-title":"Inclusion of patients with chronic kidney disease in randomized phase 3 clinical trials in patients with prostate, breast, lung, and colorectal cancer","volume":"12","author":"Delaye","year":"2023","journal-title":"Cancer Med"},{"key":"2025062821092272400_CIT0010","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jacasi.2021.04.007","article-title":"Epidemiological features of cardiovascular disease in Asia","volume":"1","author":"Zhao","year":"2021","journal-title":"JACC Asia"},{"key":"2025062821092272400_CIT0011","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1093\/eurheartj\/ehaa884","article-title":"The risk of cardiac events in patients receiving immune checkpoint inhibitors: a nationwide Danish study","volume":"42","author":"D\u2019Souza","year":"2021","journal-title":"Eur Heart J"},{"key":"2025062821092272400_CIT0012","doi-asserted-by":"publisher","first-page":"100252","DOI":"10.1016\/j.esmoop.2021.100252","article-title":"Cardiovascular adverse events are associated with usage of immune checkpoint inhibitors in real-world clinical data across the United States","volume":"6","author":"Jain","year":"2021","journal-title":"ESMO Open"},{"key":"2025062821092272400_CIT0013","doi-asserted-by":"publisher","first-page":"58","DOI":"10.37737\/ace.24009","article-title":"A new electronic medical record database linked to claims data and discharge abstract data (the RWD database) in Japan: Study design and profile","volume":"6","author":"Okumura","year":"2024","journal-title":"Ann Clin Epidemiol"},{"key":"2025062821092272400_CIT0014","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2188\/jea.JE20200288","article-title":"History and profile of Diagnosis Procedure Combination (DPC): development of a real data collection system for acute inpatient care in Japan","volume":"31","author":"Hayashida","year":"2021","journal-title":"J Epidemiol"},{"key":"2025062821092272400_CIT0015","doi-asserted-by":"publisher","first-page":"102016","DOI":"10.1016\/j.canep.2021.102016","article-title":"Validity of initial cancer diagnoses in the Diagnosis Procedure Combination data in Japan","volume":"74","author":"Shigemi","year":"2021","journal-title":"Cancer Epidemiol"},{"key":"2025062821092272400_CIT0016","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.1016\/j.jacc.2018.02.037","article-title":"Myocarditis in patients treated with immune checkpoint inhibitors","volume":"71","author":"Mahmood","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"2025062821092272400_CIT0017","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1007\/s11912-023-01414-4","article-title":"Risk factors for immune checkpoint inhibitor-mediated cardiovascular toxicities","volume":"25","author":"Yousif","year":"2023","journal-title":"Curr Oncol Rep"},{"key":"2025062821092272400_CIT0018","doi-asserted-by":"publisher","first-page":"e16373","DOI":"10.1016\/j.heliyon.2023.e16373","article-title":"Cardiovascular events after the initiation of immune checkpoint inhibitors","volume":"9","author":"Suzuki","year":"2023","journal-title":"Heliyon"},{"key":"2025062821092272400_CIT0019","doi-asserted-by":"publisher","first-page":"e000261","DOI":"10.1136\/jitc-2019-000261","article-title":"Late cardiac adverse events in patients with cancer treated with immune checkpoint inhibitors","volume":"8","author":"Dolladille","year":"2020","journal-title":"J ImmunoTher Cancer"},{"key":"2025062821092272400_CIT0020","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1038\/s41569-023-00986-9","article-title":"Immune checkpoints in cardiac physiology and pathology: therapeutic targets for heart failure","volume":"21","author":"Gergely","year":"2024","journal-title":"Nat Rev Cardiol"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/30\/6\/oyaf151\/63551646\/oyaf151.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/30\/6\/oyaf151\/63551646\/oyaf151.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T01:09:28Z","timestamp":1751159368000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/doi\/10.1093\/oncolo\/oyaf151\/8171908"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":20,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6,4]]}},"URL":"https:\/\/doi.org\/10.1093\/oncolo\/oyaf151","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,6]]},"published":{"date-parts":[[2025,6]]},"article-number":"oyaf151"}}