{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T13:34:04Z","timestamp":1771335244840,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T00:00:00Z","timestamp":1701993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors (TKIs) and anti\u2010angiogenics, are first\u2010line therapies for advanced and metastatic hepatocellular carcinoma. Although TKIs have a greater potential for off\u2010target adverse effects compared with bevacizumab (anti\u2010angiogenics), a direct comparison of the risk of cardiovascular adverse events between these two types of therapies has not been performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To compare the incidence of and characterize cardiovascular adverse events in patients with hepatocellular carcinoma receiving TKIs versus bevacizumab.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This cohort study included adult patients with hepatocellular carcinoma who received first\u2010line TKIs (sorafenib or lenvatinib) or bevacizumab at two academic medical centers and one community cancer center from September 2018 to August 2021. The primary outcome was risk of cardiovascular adverse events. Major secondary outcomes included the incidence of individual types of cardiovascular adverse events and risk factors associated with major adverse cardiovascular events (MACE).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study included 221 patients (159 TKI patients; 62 bevacizumab patients). At a median follow\u2010up of 5\u2009months, the probability of cardiovascular adverse events was not significantly different between the two groups (hazard ratio [HR]: 0.85; 95% confidence interval [95% CI]: 0.58\u20131.24; <jats:italic>p<\/jats:italic>\u2009=\u20090.390). The cumulative incidence of cardiovascular events was highest in patients receiving lenvatinib (sub\u2010distribution hazard ratio [SHR]: 1.53; 95% CI: 1.02\u20132.30) compared with those receiving sorafenib (reference) or bevacizumab (SHR: 1.05; 95% CI: 0.68\u20131.64) after adjustment for comorbidities, liver transplant status, and presence of portal vein thrombosis at baseline. Cardiovascular adverse events were observed in 151 (68%) patients, and MACE were observed in 27 (12%) patients. Risk factors associated with MACE were hypertension (SHR: 3.5; 95% CI: 0.9087\u201315.83; <jats:italic>p<\/jats:italic>\u2009=\u20090.086), prior history of MACE (SHR: 2.01; 95% CI: 0.83\u20134.87; <jats:italic>p<\/jats:italic>\u2009=\u20090.124), and tobacco use (SHR: 2.85; 95% CI: 0.90\u20138.97; <jats:italic>p<\/jats:italic>\u2009=\u20090.074).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Cardiovascular risk was not significantly different between TKIs and bevacizumab. Lenvatinib appears to have the highest risk of cardiovascular adverse events among these first\u2010line VEGF inhibitors.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.2896","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T11:47:17Z","timestamp":1701085637000},"page":"214-223","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cardiovascular adverse events in patients with hepatocellular carcinoma receiving vascular endothelial growth factor inhibitors"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6329-8383","authenticated-orcid":false,"given":"Fangzheng","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Pharmacy University of Alabama at Birmingham Hospital  Birmingham Alabama USA"},{"name":"Department of Research Baptist Hospitals of Southeast Texas  Beaumont Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carrie","family":"Lenneman","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Alabama at Birmingham School of Medicine  Birmingham Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2002-9946","authenticated-orcid":false,"given":"Ronald","family":"Krone","sequence":"additional","affiliation":[{"name":"Division of Cardiology Washington University in St. Louis School of Medicine  St. Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4294-5232","authenticated-orcid":false,"given":"Grant R.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Alabama at Birmingham School of Medicine  Birmingham Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9618-6935","authenticated-orcid":false,"suffix":"Jr","given":"Darryl","family":"Outlaw","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Alabama at Birmingham School of Medicine  Birmingham Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8265-7713","authenticated-orcid":false,"given":"Michael","family":"Katsnelson","sequence":"additional","affiliation":[{"name":"Division of Cardiology Washington University in St. Louis School of Medicine  St. Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8056-3134","authenticated-orcid":false,"given":"Stephen","family":"Lirette","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Alabama at Birmingham Hospital  Birmingham Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,12,8]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"National Cancer Institute.Cancer stat facts: liver and intrahepatic bile duct cancer. 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