{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:35:36Z","timestamp":1785429336339,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,2]]},"group-title":"Oncology","reference-count":10,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["Cedars-Sinai Cancer Center Developmental Funds (No Award Number)"],"award-info":[{"award-number":["Cedars-Sinai Cancer Center Developmental Funds (No Award Number)"]}],"id":[{"id":"https:\/\/ror.org\/02pammg90","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Androgen receptor pathway inhibitors (ARPIs) have transformed the treatment of high risk and metastatic prostate cancer, though are associated with increased cardiovascular risk. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been shown to reduce cardiovascular events in non-cancer populations, but their role in patients receiving ARPIs is unclear.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Retrospective analysis of 120 men with PC treated with ARPIs between 2015-2025 with any GLP-1 RA exposure. The time of GLP-1 RA use was categorized relative to ARPI initiation (pre- vs post-ARPI). Cumulative incidences for major adverse cardiac events (MACE) any grade 2 or greater cardiac common terminology criteria for adverse events (CTCAE) were estimated. Fine-Gray regressions were performed (non-cardiac death as a competing risk).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The median follow-up was 2.3 years (interquartile range [IQR] 1.3-3.7). The median age was 72 years (IQR 66-78). Atherosclerotic cardiovascular disease (ASCVD) was present in 45.0% (n=54). Overall, 55.0% (n=66) initiated GLP-1 RA therapy prior to ARPI and 45.0% (n=54) after ARPI initiation, with a median duration of GLP-1 RA use of 4.0 years (IQR, 2.3-7.0) and 1.3 years (IQR, 0.6-2.1), respectively. Four patients experienced MACE, including three coronary revascularizations and one ischemic stroke. 25 patients experienced at least one grade 2 or greater cardiac event, most commonly arrhythmia (n=20) and thromboembolic disease (n=11). The 2-year cumulative incidence of MACE and grade \u22652 cardiac events was 1.7% and 16.1%, respectively. Adjusting for pre-existing cardiovascular risk, GLP-1 RA duration, and pre- ARPI androgen deprivation therapy use, GLP-1RA use prior to ARPI initiation (vs. after ARPI start) was associated with reduced risk of grade \u22652 cardiac events (subdistribution hazard ratio 0.26, 95% CI 0.08-0.91; p=0.036).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>GLP-1 RA use prior to ARPI initiation was associated with reduced risk of cardiac events, suggesting that earlier metabolic optimization may influence cardiovascular outcomes. These hypothesis-generating findings support investigation of early GLP-1 RA initiation as a potential cardiovascular risk mitigation strategy during ARPI therapy.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.26.26353962","type":"posted-content","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T05:10:21Z","timestamp":1780463421000},"source":"Crossref","is-referenced-by-count":0,"title":["GLP-1 Receptor Agonists and Cardiovascular Events During Androgen Receptor Pathway Inhibitor Therapy"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3165-4803","authenticated-orcid":false,"given":"Katelyn M","family":"Atkins","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA"},{"name":"Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil","family":"Chakravarty","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Oorloff","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giana","family":"Grigsby","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irfan","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell","family":"Kamrava","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andriana","family":"Nikolova","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Karlstaedt","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody","family":"Ramin","sequence":"additional","affiliation":[{"name":"Department of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie K.","family":"Ballas","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"11","key":"2026060511051173000_2026.05.26.26353962v1.1","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1002\/cncr.35285","article-title":"A practical guide for assessing and managing cardiovascular risk during androgen-deprivation therapy in patients with prostate cancer","volume":"130","year":"2024","journal-title":"Cancer"},{"key":"2026060511051173000_2026.05.26.26353962v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41391-020-00275-3"},{"key":"2026060511051173000_2026.05.26.26353962v1.3","doi-asserted-by":"crossref","unstructured":"Omar El-Taji , Samih Taktak , Craig Jones , Mick Brown , Noel Clarke , Ashwin Sachdeva . 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