{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:10:14Z","timestamp":1791267014177,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T00:00:00Z","timestamp":1620864000000},"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":["Cancer Medicine"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cardiovascular adverse events (CVAEs) associated with BRAF inhibitors alone versus combination BRAF\/MEK inhibitors are not fully understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study included all adult patients who received BRAF inhibitors (vemurafenib, dabrafenib, encorafenib) or combinations BRAF\/MEK inhibitors (vemurafenib\/cobimetinib; dabrafenib\/trametinib; encorafenib\/binimetinib). We utilized the cross\u2010sectional FDA\u2019s Adverse Events Reporting System (FAERS) and longitudinal Truven Health Analytics\/IBM MarketScan database from 2011 to 2018. Various CVAEs, including arterial hypertension, heart failure (HF), and venous thromboembolism (VTE), were studied using adjusted regression techniques.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In FAERS, 7752 AEs were reported (40% BRAF and 60% BRAF\/MEK). Median age was 60 (IQR 49\u201369) years with 45% females and 97% with melanoma. Among these, 567 (7.4%) were cardiovascular adverse events (mortality rate 19%). Compared with monotherapy, combination therapy was associated with increased risk for HF (reporting odds ratio [ROR]\u00a0=\u00a01.62 (CI\u00a0=\u00a01.14\u20132.30);\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.007), arterial hypertension (ROR\u00a0=\u00a01.75 (CI\u00a0=\u00a01.12\u20132.89);\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.02) and VTE (ROR\u00a0=\u00a01.80 (CI\u00a0=\u00a01.12\u20132.89);\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.02). Marketscan had 657 patients with median age of 53\u00a0years (IQR 46\u201360), 39.3% female, and 88.7% with melanoma. There were 26.2% CVAEs (CI: 14.8%\u201336%) within 6\u00a0months of medication start in those receiving combination therapy versus 16.7% CVAEs (CI: 13.1%\u201320.2%) among those receiving monotherapy. Combination therapy was associated with CVAEs compared to monotherapy (adjusted HR: 1.56 (CI: 1.01\u20132.42);\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.045).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>In two independent real\u2010world cohorts, combination BRAF\/MEK inhibitors were associated with increased CVAEs compared to monotherapy, especially HF, and hypertension.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.3938","type":"journal-article","created":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T06:40:56Z","timestamp":1620888056000},"page":"3862-3872","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Cardiovascular adverse events associated with BRAF versus BRAF\/MEK inhibitor: Cross\u2010sectional and longitudinal analysis using two large national registries"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0253-1174","authenticated-orcid":false,"given":"Avirup","family":"Guha","sequence":"first","affiliation":[{"name":"Harrington Heart and Vascular Institute University Hospitals Case Western Reserve University Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prantesh","family":"Jain","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology University Hospitals Cleveland Medical Center Seidman Cancer Center at Case Comprehensive Cancer Center Case Western Reserve University Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Fradley","sequence":"additional","affiliation":[{"name":"Cardio\u2010Oncology Program Division of Cardiology University of Pennsylvania Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Lenihan","sequence":"additional","affiliation":[{"name":"Cardio\u2010Oncology Center of Excellence Division of Cardiology Washington University in St Louis St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jahir M.","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"Layer6 Inc. Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chhavi","family":"Jain","sequence":"additional","affiliation":[{"name":"Lerner Research Institute Cleveland Clinic Case Comprehensive Cancer Center Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","family":"de Lima","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology University Hospitals Cleveland Medical Center Seidman Cancer Center at Case Comprehensive Cancer Center Case Western Reserve University Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6190-9304","authenticated-orcid":false,"given":"Jill S.","family":"Barnholtz\u2010Sloan","sequence":"additional","affiliation":[{"name":"Department of Population and Quantitative Health Sciences Case Comprehensive Cancer Center Case Western Reserve University School of Medicine Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme H.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences Cardio\u2010Oncology Program University of South Florida Tampa General Hospital and Moffitt Cancer Center Tampa FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4535-6839","authenticated-orcid":false,"given":"Afshin","family":"Dowlati","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology University Hospitals Cleveland Medical Center Seidman Cancer Center at Case Comprehensive Cancer Center Case Western Reserve University Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadeer","family":"Al\u2010Kindi","sequence":"additional","affiliation":[{"name":"Harrington Heart and Vascular Institute University Hospitals Case Western Reserve University Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103782"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-3122"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1412690"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30497-2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1708539"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx176"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30122-X"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1408868"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30142-6"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5853"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.8890"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehy453"},{"key":"e_1_2_9_14_1","unstructured":"NCI.Comorbidity SAS Macro (2014 version).https:\/\/healthcaredelivery.cancer.gov\/seermedicare\/considerations\/macro\u20102014.html."},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2018.06.005"},{"key":"e_1_2_9_16_1","first-page":"172","article-title":"Osimertinib\u2010induced cardiotoxicity. 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