{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:32:52Z","timestamp":1791261172969,"version":"4.1.0"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,6,20]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Cyclin\u2010dependent kinase (CDK) 4 and 6 inhibitors have significantly improved survival in patients with hormone receptor\u2013positive metastatic breast cancer. There are few data regarding the epidemiology of cardiovascular adverse events (CVAEs) with these therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Using the OneFlorida Data Trust, adult patients without prior cardiovascular disease who received at least 1 CDK4\/6 inhibitor were included in the analysis. CVAEs identified from\n                      <jats:italic>International Classification of Diseases<\/jats:italic>\n                      ,\n                      <jats:italic>Ninth<\/jats:italic>\n                      and\n                      <jats:italic>Tenth Revisions<\/jats:italic>\n                      (\n                      <jats:italic>ICD\u20109\/10<\/jats:italic>\n                      ) codes included hypertension, atrial fibrillation(AF)\/atrial flutter (AFL), heart failure\/cardiomyopathy, ischemic heart disease, and pericardial disease. Competing risk analysis (Fine\u2013Gray model) was used to determine the association between CDK4\/6 inhibitor therapy and incident CVAEs. The effect of CVAEs on all\u2010cause death was studied using Cox proportional hazard models. Propensity\u2010weight analyses were performed to compare these patients to a cohort of patients treated with anthracyclines. A total of 1376 patients treated with CDK4\/6 inhibitors were included in the analysis. CVAEs occurred in 24% (35.9 per 100 person\u2010years). CVAEs were slightly higher in patients who received CKD4\/6 inhibitors compared with anthracyclines (\n                      <jats:italic>P<\/jats:italic>\n                      =0.063), with higher death rate associated with the development of AF\/AFL or cardiomyopathy\/heart failure in the CDK4\/6 group. The development of cardiomyopathy\/heart failure and AF\/AFL was associated with increased all\u2010cause death (adjusted hazard ratio [HR], 4.89 [95% CI, 2.98\u20138.05]; and 5.88 [95% CI, 3.56\u20139.73], respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">CVAEs may be more common with CDK4\/6 inhibitors than previously recognized, with increased death rates in these patients who develop AF\/AFL or heart failure. Further research is needed to definitively determine cardiovascular risk associated with these novel anticancer treatments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.123.029361","type":"journal-article","created":{"date-parts":[[2023,6,10]],"date-time":"2023-06-10T22:25:20Z","timestamp":1686435920000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":63,"title":["Adverse Cardiovascular Events Associated With Cyclin\u2010Dependent Kinase 4\/6 Inhibitors in Patients With Metastatic Breast Cancer"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8352-8975","authenticated-orcid":false,"given":"Michael G.","family":"Fradley","sequence":"first","affiliation":[{"name":"Cardio\u2010Oncology Center of Excellence, Division of Cardiology, Department of Medicine Perelman School of Medicine at the University of Pennsylvania Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3036-4748","authenticated-orcid":false,"given":"Nam H. 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Oncology Perelman School of Medicine at the University of Pennsylvania Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7374-7330","authenticated-orcid":false,"given":"Igor","family":"Makhlin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology &amp; Oncology Perelman School of Medicine at the University of Pennsylvania Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9183-9340","authenticated-orcid":false,"given":"Susan","family":"Dent","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Duke University Durham NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8587-7279","authenticated-orcid":false,"given":"Benedicte","family":"Lefebvre","sequence":"additional","affiliation":[{"name":"Cardio\u2010Oncology Center of Excellence, Division of Cardiology, Department of Medicine Perelman School of Medicine at the University of Pennsylvania Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8804-0653","authenticated-orcid":false,"given":"Joseph","family":"Carver","sequence":"additional","affiliation":[{"name":"Cardio\u2010Oncology Center of Excellence, Division of Cardiology, Department of Medicine Perelman School of Medicine at the University of Pennsylvania Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenica N.","family":"Upshaw","sequence":"additional","affiliation":[{"name":"Cardio\u2010Oncology Program, Division of Cardiology Tufts Medical Center Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2207-9552","authenticated-orcid":false,"given":"David","family":"DeRemer","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research College of Pharmacy, University of Florida Gainesville FL"},{"name":"Center for Pharmacogenomics and Precision Medicine, College of Pharmacy University of Florida Gainesville FL"},{"name":"UF Health Cancer Center Gainesville FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6628-9981","authenticated-orcid":false,"given":"Bonnie","family":"Ky","sequence":"additional","affiliation":[{"name":"Cardio\u2010Oncology Center of Excellence, Division of Cardiology, Department of Medicine Perelman School of Medicine at the University of Pennsylvania Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0253-1174","authenticated-orcid":false,"given":"Avirup","family":"Guha","sequence":"additional","affiliation":[{"name":"Cardio\u2010Oncology Program, Division of Cardiology, Department of Internal Medicine Medical College of Georgia at Augusta University Augusta GA"},{"name":"Cardio\u2010Oncology Program, Division of Cardiology The Ohio State University Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8218-1620","authenticated-orcid":false,"given":"Yan","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research College of Pharmacy, University of Florida Gainesville FL"},{"name":"Center for Pharmacogenomics and Precision Medicine, College of Pharmacy University of Florida Gainesville FL"},{"name":"UF Health Cancer Center Gainesville FL"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/35106065"},{"key":"e_1_3_2_3_2","first-page":"2127","article-title":"Expression and amplification of cyclin genes in human breast cancer","volume":"8","author":"Buckley MF","year":"1993","unstructured":"Buckley MF, Sweeney KJ, Hamilton JA, Sini RL, Manning DL, Nicholson RI, de Fazio A, Watts CK, Musgrove EA, Sutherland RL. 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