{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T14:44:39Z","timestamp":1793371479167,"version":"4.5.0"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T00:00:00Z","timestamp":1708992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>A diagnosis of epilepsy has been associated with adverse cardiovascular events (CEs), but the extent to which antiseizure medications (ASMs) may contribute to this is not well understood. The aim of this study was to compare the risk of adverse CEs associated with ASM in patients with epilepsy (PWE).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective case\u2013control cohort study was conducted using TriNetX, a global health federated network of anonymized patient records. Patients older than 18\u2009years, with a diagnosis of epilepsy (International Classification of Diseases, 10th Revision code G40) and a medication code of carbamazepine, lamotrigine, or valproate were compared. Patients with cardiovascular disease prior to the diagnosis of epilepsy were excluded. Cohorts were 1:1 propensity score matched (PSM) according to age, sex, ethnicity, hypertension, heart failure, atherosclerotic heart disease, atrial and cardiac arrythmias, diabetes, disorders of lipoprotein metabolism, obesity, schizophrenia and bipolar disorder, medications, and epilepsy classification. The primary outcome was a composite of adverse CEs (ischemic stroke, acute ischemic heart disease, and heart failure) at 10\u2009years. Cox regression analyses were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) following 1:1 PSM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 374\u2009950 PWE included; three cohorts were established after PSM: (1) carbamazepine compared to lamotrigine, <jats:italic>n<\/jats:italic>\u2009=\u20094722, mean age 37.4\u2009years; (2) valproate compared to lamotrigine, <jats:italic>n<\/jats:italic>\u2009=\u20095478, mean age 33.9\u2009years; and (3) valproate compared to carbamazepine, <jats:italic>n<\/jats:italic>\u2009=\u20094544, mean age 37.0\u2009years. Carbamazepine and valproate use were associated with significantly higher risk of composite cardiovascular outcome compared to lamotrigine (HR\u2009=\u20091.390, 95% CI\u2009=\u20091.160\u20131.665 and HR\u2009=\u20091.264, 95% CI\u2009=\u20091.050\u20131.521, respectively). Valproate was associated with a 10\u2010year higher risk of all\u2010cause death than carbamazepine (HR\u2009=\u20091.226, 95% CI\u2009=\u20091.017\u20131.478), but risk of other events was not significantly different.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Carbamazepine and valproate were associated with increased CE risks compared to lamotrigine. Cardiovascular risk factor monitoring and careful follow\u2010up should be considered for these patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17922","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T11:49:32Z","timestamp":1709034572000},"page":"1264-1274","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Association of antiseizure medications and adverse cardiovascular events: A global health federated network analysis"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9662-2845","authenticated-orcid":false,"given":"Josephine","family":"Mayer","sequence":"first","affiliation":[{"name":"Liverpool Centre of Cardiovascular Science University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital  Liverpool UK"},{"name":"Department of Pharmacology and Therapeutics, Institute of Systems, Molecular, and Integrative Biology University of Liverpool  Liverpool UK"},{"name":"Department of Neurology The Walton Centre, National Health Service Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9588-2944","authenticated-orcid":false,"given":"Gashirai K.","family":"Mbizvo","sequence":"additional","affiliation":[{"name":"Liverpool Centre of Cardiovascular Science University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital  Liverpool UK"},{"name":"Department of Pharmacology and Therapeutics, Institute of Systems, Molecular, and Integrative Biology University of Liverpool  Liverpool UK"},{"name":"Department of Neurology The Walton Centre, National Health Service Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Bucci","sequence":"additional","affiliation":[{"name":"Liverpool Centre of Cardiovascular Science University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital  Liverpool UK"},{"name":"Department of General and Specialized Surgery Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Marson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Institute of Systems, Molecular, and Integrative Biology University of Liverpool  Liverpool UK"},{"name":"Department of Neurology The Walton Centre, National Health Service Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory Y. H.","family":"Lip","sequence":"additional","affiliation":[{"name":"Liverpool Centre of Cardiovascular Science University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital  Liverpool UK"},{"name":"Department of Clinical Medicine, Danish Center for Health Services Research Aalborg University  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2018.09.009"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002984"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2021.108393"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpcardiol.2023.101868"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2020.106946"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2021.107878"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2019.12.001"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1684\/epd.2021.1360"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2019.05.005"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12475"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21615"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3988\/jcn.2017.13.4.371"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000426"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2006.02.008"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/jamiaopen\/ooad035"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215\u20100366(21)00084\u20105"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2021.4584"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2021.07.020"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl\u20102014\u2010305664"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3109\/07853890.2016.1140225"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2021.3424"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16930"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2023.109496"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17339"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200164"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17696"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528\u20101167.2011.03316.x"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528\u20101157.1999.tb00744.x"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1993.00540060030012"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2015.03.002"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14554"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16745"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16547"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.17922","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T14:55:56Z","timestamp":1716216956000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.17922"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,27]]},"references-count":33,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1111\/epi.17922"],"URL":"https:\/\/doi.org\/10.1111\/epi.17922","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,27]]},"assertion":[{"value":"2023-11-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}