{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:12:15Z","timestamp":1768569135865,"version":"3.49.0"},"posted":{"date-parts":[[2025,8,5]]},"group-title":"Cardiovascular Medicine","reference-count":20,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,8,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Cyclin-dependent kinase 4\/6 (CDK4\/6) inhibitors are increasingly used in hormone receptor-positive, HER2-negative (HR+\/HER2\u2212) breast cancer, yet emerging data suggest potential cardiotoxicity, including atrial arrhythmias (AA). Understanding the incidence and outcomes of AA in this population is essential as indications for CDK4\/6 inhibitors expand.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To evaluate the incidence of new-onset AA and associated outcomes in patients with HR+\/HER2\u2212 breast cancer treated with CDK4\/6 inhibitors.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a retrospective cohort study of patients treated at Mayo Clinic from 2015\u2013 2024 who received CDK4\/6 inhibitors for HR+\/HER2\u2212 breast cancer. The primary outcome was incidence of AA (atrial fibrillation, atrial flutter, or atrial tachycardia). Secondary outcomes included cerebrovascular events and all-cause mortality. Kaplan-Meier estimates and Cox regression models were used to assess outcomes and associated risk factors.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among 2,782 patients, 59% received palbociclib, 28% abemaciclib, and 14% ribociclib.<\/jats:p>\n                  <jats:p>New-onset AA occurred in 45, with cumulative incidence at 5 years of 2.8%. No significant differences in AA incidence were observed between agents (p=0.44). Multivariate analysis identified age at treatment as the only independent predictor of AA (HR 1.073, p&lt;0.001). Four patients with new-onset AA experienced cerebrovascular events. New-onset AA was associated with increased mortality (HR 1.56, p=0.012).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>CDK4\/6 inhibitor therapy was associated with a low but clinically significant risk of new-onset AA, which in turn is associated with increased mortality. There was no significant difference in new-onset AA risk between different individual CDK4\/6 inhibitor agents.<\/jats:p>\n                  <jats:p>Prospective studies are needed to define mechanisms and guide monitoring strategies.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.08.01.25332600","type":"posted-content","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T03:20:15Z","timestamp":1754450415000},"source":"Crossref","is-referenced-by-count":0,"title":["Incidence and Outcomes of Atrial Arrhythmia with CDK4\/6 Inhibitors in HR-Positive \/ HER2-Negative Breast Cancer"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5656-5571","authenticated-orcid":false,"given":"Nathaniel E.","family":"Davis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joerg","family":"Herrmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5148-9174","authenticated-orcid":false,"given":"David O.","family":"Hodge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophia","family":"Blumenfeld","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn J.","family":"Ruddy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0365-9471","authenticated-orcid":false,"given":"Nicholas Y.","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025080703551284000_2025.08.01.25332600v1.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2114663"},{"key":"2025080703551284000_2025.08.01.25332600v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(22)00694-5"},{"key":"2025080703551284000_2025.08.01.25332600v1.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1810527"},{"key":"2025080703551284000_2025.08.01.25332600v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(22)00694-5"},{"key":"2025080703551284000_2025.08.01.25332600v1.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2305488"},{"key":"2025080703551284000_2025.08.01.25332600v1.6","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvz020"},{"key":"2025080703551284000_2025.08.01.25332600v1.7","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.123.029361"},{"key":"2025080703551284000_2025.08.01.25332600v1.8","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2020.38.15_suppl.e13038"},{"key":"2025080703551284000_2025.08.01.25332600v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-020-0348-1"},{"key":"2025080703551284000_2025.08.01.25332600v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaccao.2021.01.009"},{"key":"2025080703551284000_2025.08.01.25332600v1.11","unstructured":"fda, cder. 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