{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T13:28:10Z","timestamp":1772976490043,"version":"3.50.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:00:00Z","timestamp":1659484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004606","name":"Chang Gung Medical Foundation","doi-asserted-by":"publisher","award":["CMRPD1K0022"],"award-info":[{"award-number":["CMRPD1K0022"]}],"id":[{"id":"10.13039\/501100004606","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004606","name":"Chang Gung Medical Foundation","doi-asserted-by":"publisher","award":["NMRPD1K0771"],"award-info":[{"award-number":["NMRPD1K0771"]}],"id":[{"id":"10.13039\/501100004606","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 109-2314-B-182-035"],"award-info":[{"award-number":["MOST 109-2314-B-182-035"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Patients with colorectal cancer (CRC) are more likely to develop cardiovascular disease (CVD) than those without cancer. Little is known regarding their CV risk after operative chemotherapy. We aimed to compare the risk of CV disease among different fluoropyrimidine derivatives.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We assembled a nationwide cohort of patients with newly diagnosed CRC between 2004 and 2015 who received fluoropyrimidine-based adjuvant chemotherapy for resected CRC by linking the Taiwan Cancer Registry (TCR), National Health Insurance Research Database (NHIRD), and Taiwan Death Registry (TDR). All eligible patients were followed from CRC diagnosis (index date) until a CV event, death, loss to follow-up, or December 31st 2018, whichever came first. CV outcomes included acute myocardial infarction (AMI), life-threatening arrhythmia (LTA), congestive heart failure (CHF), and ischemic stroke (IS). We used stabilized inverse probability of treatment weighting using propensity score (SIPTW) to balance all covariates among the three chemotherapy groups: tegafur-uracil (UFT), non-UFT, and mixed. In addition, survival analysis was conducted to examine the association between study outcomes and chemotherapy groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>From 2004 to 2015, 10,615 (32.8%) patients received UFT alone, 14,511 (44.8%) patients received non-UFT, and 7,224 (22.3%) patients received mixed chemotherapy. After SIPTW, the UFT group had significantly lower all-cause mortality and cancer-related death rates than the other two chemotherapy groups. However, the UFT group had significantly higher rates of cancer death, ischemic stroke, and heart failure than those of the other two chemotherapy groups. The UFT group also had a significantly higher AMI rate than the mixed group. There was no significant difference in LTA among the three groups. Similar findings were observed in the subgroup analysis (stage II and age &amp;lt;70 years, stage II and age \u226570 years, stage III and age &amp;lt;70 years, stage III and age \u226570 years) as the overall population was observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Higher heart failure and ischemic stroke rates were found in the UFT group than in the other two chemotherapy groups, especially those with stage III CRC and \u226570 years of age. Careful monitoring of this subset of patients when prescribing UFT is warranted.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2022.880956","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T04:47:30Z","timestamp":1659502050000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Risk of cardiovascular disease among different fluoropyrimidine-based chemotherapy regimens as adjuvant treatment for resected colorectal cancer"],"prefix":"10.3389","volume":"9","author":[{"given":"Wen-Kuan","family":"Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Pang","family":"Ho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hung-Chih","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu-Hao","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Yi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Chi","family":"Chou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei-Hung","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jen-Shi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsai-Sheng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lai-Chu","family":"See","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"271","DOI":"10.3322\/caac.21349","article-title":"Cancer treatment and survivorship statistics, 2016","volume":"66","author":"Miller","year":"2016","journal-title":"CA Cancer J Clin."},{"key":"B2","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1158\/1055-9965.EPI-12-1356","article-title":"Cancer survivors in the United States: prevalence across the survivorship trajectory and implications for care","volume":"22","author":"de Moor","year":"2013","journal-title":"Cancer Epidemiol Biomarkers Prev."},{"key":"B3","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1007\/s11764-016-0584-x","article-title":"Cardiovascular disease and physical activity in adult cancer survivors: a nested, retrospective study from the Atlantic PATH cohort","volume":"11","author":"Keats","year":"2017","journal-title":"J Cancer Surviv."},{"key":"B4","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1093\/annonc\/mdw604","article-title":"Causes of death among cancer patients","volume":"28","author":"Zaorsky","year":"2016","journal-title":"Ann Oncol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1200\/JCO.2015.64.0409","article-title":"Cardiovascular disease among survivors of adult-onset cancer: a community-based retrospective cohort study","volume":"34","author":"Armenian","year":"2016","journal-title":"J Clin Oncol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1001\/jamaoncol.2019.0676","article-title":"Obesity and the importance of cardiovascular disease surveillance after colorectal cancer","volume":"5","author":"Passarelli","year":"2019","journal-title":"JAMA Oncol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1200\/JCO.2017.74.9739","article-title":"New-onset cardiovascular morbidity in older adults with stage I to III colorectal cancer","volume":"36","author":"Kenzik","year":"2018","journal-title":"J Clin Oncol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"21359","DOI":"10.1038\/s41598-021-00735-3","article-title":"Cardiovascular morbidities in postoperative colorectal cancer patients","volume":"11","author":"Kim","year":"2021","journal-title":"Sci Rep."},{"key":"B9","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s12885-019-6508-1","article-title":"Effect of adjuvant chemotherapy on survival benefit in stage III colon cancer patients stratified by age: a Japanese real-world cohort study","volume":"20","author":"Kawamura","year":"2020","journal-title":"BMC Cancer."},{"key":"B10","doi-asserted-by":"publisher","first-page":"4157","DOI":"10.7150\/jca.42404","article-title":"Outcomes of adjuvant oral versus intravenous fluoropyrimidines for high-risk stage II or stage III colon adenocarcinoma: a propensity score-matched, nationwide, population-based cohort study","volume":"11","author":"Zhang","year":"2020","journal-title":"J Cancer."},{"key":"B11","doi-asserted-by":"publisher","first-page":"103346","DOI":"10.1016\/j.critrevonc.2021.103346","article-title":"Risk factors of fluoropyrimidine induced cardiotoxicity among cancer patients: a systematic review and meta-analysis","volume":"162","author":"Li","year":"2021","journal-title":"Crit Rev Oncol Hematol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1111\/tri.13081","article-title":"An unjustified benefit: immortal time bias in the analysis of time-dependent events","volume":"31","author":"Gleiss","year":"2018","journal-title":"Transpl Int."},{"key":"B13","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1111\/j.1524-4733.2009.00671.x","article-title":"Use of stabilized inverse propensity scores as weights to directly estimate relative risk and its confidence intervals","volume":"13","author":"Xu","year":"2010","journal-title":"Value Health."},{"key":"B14","doi-asserted-by":"publisher","first-page":"3388","DOI":"10.1002\/sim.5753","article-title":"A tutorial on propensity score estimation for multiple treatments using generalized boosted models","volume":"32","author":"McCaffrey","year":"2013","journal-title":"Stat Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e18174","DOI":"10.1371\/journal.pone.0018174","article-title":"Weight trimming and propensity score weighting","volume":"6","author":"Lee","year":"2011","journal-title":"PLoS ONE."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1080\/03610910902859574","article-title":"Using the standardized difference to compare the prevalence of a binary variable between two groups in observational research","volume":"38","author":"Austin","year":"2009","journal-title":"Commun Stat Simul Comp."},{"key":"B17","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1111\/j.2517-6161.1972.tb00899.x","article-title":"Regression models and life-tables","volume":"34","author":"Cox","year":"1972","journal-title":"J Royal Stat Soc Series B."},{"key":"B18","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1093\/aje\/kwp107","article-title":"Competing risk regression models for epidemiologic data","volume":"170","author":"Lau","year":"2009","journal-title":"Am J Epidemiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1002\/sim.5984","article-title":"The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments","volume":"33","author":"Austin","year":"2014","journal-title":"Stat Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1002\/sim.4780141510","article-title":"Graphical methods for assessing violations of the proportional hazards assumption in Cox regression","volume":"14","author":"Hess","year":"1995","journal-title":"Stat Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1007\/s11605-011-1682-8","article-title":"Postoperative adjuvant chemotherapy for stage II colorectal cancer: a systematic review of 12 randomized controlled trials","volume":"16","author":"Wu","year":"2012","journal-title":"J Gastrointest Surg."},{"key":"B22","unstructured":"NCCN Guidelines for Patients: Rectal Cancer, 20212021"},{"key":"B23","unstructured":"NCCN Guidelines for Patients: Rectal Cancer, 20212021"},{"key":"B24","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/2050-6511-15-47","article-title":"A systematic review of the pathophysiology of 5-fluorouracil-induced cardiotoxicity","volume":"15","author":"Polk","year":"2014","journal-title":"BMC Pharmacol Toxicol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1038\/sj.bjc.6690098","article-title":"Dihydropyrimidine dehydrogenase deficiency and fluorouracil-related toxicity","volume":"79","author":"Milano","year":"1999","journal-title":"Br J Cancer."},{"key":"B26","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1007\/s10147-005-0516-7","article-title":"5-Fluorouracil cardiotoxicity induced by alpha-fluoro-beta-alanine","volume":"10","author":"Muneoka","year":"2005","journal-title":"Int J Clin Oncol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1002\/jat.1118","article-title":"Toxicology of fluoroacetate: a review, with possible directions for therapy research","volume":"26","author":"Goncharov","year":"2006","journal-title":"J Appl Toxicol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1093\/jjco\/hyi071","article-title":"Cardiotoxicity of de Gramont's regimen: incidence, clinical characteristics and long-term follow-up","volume":"35","author":"Meydan","year":"2005","journal-title":"Jpn J Clin Oncol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s00432-007-0250-9","article-title":"Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study","volume":"134","author":"Kosmas","year":"2008","journal-title":"J Cancer Res Clin Oncol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.ejca.2017.02.009","article-title":"Incidence of capecitabine-related cardiotoxicity in different treatment schedules of metastatic colorectal cancer: a retrospective analysis of the CAIRO studies of the Dutch colorectal cancer group","volume":"76","author":"Kwakman","year":"2017","journal-title":"Eur J Cancer."}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.880956\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T04:47:36Z","timestamp":1659502056000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.880956\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,3]]},"references-count":30,"alternative-id":["10.3389\/fcvm.2022.880956"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2022.880956","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,3]]},"article-number":"880956"}}