{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T15:51:28Z","timestamp":1782921088480,"version":"3.54.5"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study was designed to examine the relationship between CDK4\/6 inhibitor therapy and cardiovascular adverse events (CVAEs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>A disproportionality analysis was performed on reports from the FDA Adverse Event Reporting System (FAERS) database covering the period from 2015 to the first quarter of 2025. The reporting odds ratio (ROR) and information components (IC) were derived from this analysis. CVAEs were categorized into ten specific groups based on the standardized MedDRA queries (SMQs). Multifactorial logistic regression analysis was conducted to identify factors associated with CVAEs following treatment with CDK4\/6 inhibitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Analysis of 4,002 CVAEs associated with CDK4\/6 inhibitors indicated a stronger reporting association of cardiotoxicity for ribociclib (OR = 1.55, p &amp;lt; 0.001), especially arrhythmia. Ribociclib + fulvestrant showed a strong arrhythmia signal (ROR = 2.86; n = 188), while ribociclib + letrozole had the strongest QT prolongation signal (ROR = 6.51; n = 291) and an increased reporting signal for shock (ROR = 4.33). Abemaciclib + fulvestrant exhibited stronger thrombotic signals (ROR = 2.50) than with letrozole (ROR = 1.24). Patients over 65 showed stronger CVAE signals (OR = 1.29, p &amp;lt; 0.001), further elevated by letrozole\/fulvestrant combinations (OR = 1.83\/1.32, p &amp;lt; 0.001). Most CVAEs occurred early (0\u201360 days), with peak incidence for ribociclib + letrozole at 0\u201330 days and late arrhythmia resurgence for ribociclib + fulvestrant (210\u2013240 days). Shock-related mortality was the most fatal outcome; thrombotic events prolonged hospitalization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CDK4\/6 inhibitor combinations show notable cardiovascular reporting signals, with more frequent CVAE reports in letrozole-containing regimens. These signals suggest enhanced vigilance for thrombosis, arrhythmias, QT prolongation, and shock may be warranted. Cohort and long-term trials are needed to validate these safety findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1831639","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T15:24:00Z","timestamp":1782919440000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiovascular toxicity of CDK4\/6 inhibitors combined with endocrine therapy versus endocrine therapy alone in HR+\/HER2- breast cancer: a real-world study based on the FAERS database"],"prefix":"10.3389","volume":"17","author":[{"given":"Shuai","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Pharmacy, First Affiliated Hospital of Dalian Medical University","place":["Dalian, China"]},{"name":"College of Pharmacy, Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, First Affiliated Hospital of Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanwei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, First Affiliated Hospital of Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongshun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, First Affiliated Hospital of Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1007\/s40263-023-01052-1","article-title":"Levetiracetam interaction with direct oral anticoagulants: a pharmacovigilance study","volume":"37","author":"Abou Kaoud","year":"2023","journal-title":"CNS Drugs"},{"key":"B2","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/s41698-023-00360-5","article-title":"AKT\/mTOR signaling modulates resistance to endocrine therapy and CDK4\/6 inhibition in metastatic breast cancers","volume":"7","author":"Abu-Khalaf","year":"2023","journal-title":"NPJ Precis. 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