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We aimed to characterize the cardiovascular AEs of BTKIs reported in the US Food and Drug Administration (FDA) Adverse Event Reporting System, and to compare the cardiovascular risks of BTKIs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Across all indications of three FDA\u2010approved BTKIs, primary suspect drugs were extracted over two periods: from January 2013 to December 2022 (after the approval of the first BTKI), and from January 2020 to December 2022 (all three BTKIs on the market). Disproportionality was measured by reporting odds ratios (RORs) and information components. Additional analyses were performed without incorporating patients with underlying cardiovascular disease (CVD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 10\u2009353 cases included the uses of ibrutinib, acalabrutinib and zanubrutinib. Ibrutinib was significantly associated with 47 cardiovascular AEs. Acalabrutinib was associated with new signals, including cardiac failure (ROR\u2009=\u20091.82 [1.13\u20102.93]), pulmonary oedema (ROR\u2009=\u20092.15 [1.19\u20103.88]), ventricular extrasystoles (ROR\u2009=\u20095.18 [2.15\u201012.44]), heart rate irregular (ROR\u2009=\u20093.05 [1.53\u20106.11]), angina pectoris (ROR\u2009=\u20093.18 [1.71\u20105.91]) and cardiotoxicity (ROR\u2009=\u200925.22 [17.14\u201037.10]). In addition, cardiovascular events had an earlier onset in acalabrutinib users. Zanubrutinib was only associated with atrial fibrillation. Acalabrutinib and zanubrutinib had lower ROR values than ibrutinib. The AE signals were generally consistent between the population receiving and not receiving CVD medications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Potential cardiovascular risks identified in this study were not clearly noted on the label of marketed acalabrutinib. Caution should be paid to the cardiovascular risks of BTKIs having been or being developed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16127","type":"journal-article","created":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T05:54:31Z","timestamp":1717480471000},"page":"2166-2179","source":"Crossref","is-referenced-by-count":8,"title":["Cardiovascular events of Bruton's tyrosine kinase inhibitors: A real\u2010world study based on the United States Food and Drug Administration Adverse Event Reporting System database"],"prefix":"10.1111","volume":"90","author":[{"given":"Zeng\u2010Xiang","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, Sir Run Run Hospital Nanjing Medical University  Nanjing China"},{"name":"Department of Clinical Pharmacy, School of Basic Medical Sciences and Clinical Pharmacy China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian\u2010Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"Hubert Department of Global Health, Rollins School of Public Health Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan\u2010Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Sir Run Run Hospital Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Dongfang Hospital Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2931-798X","authenticated-orcid":false,"given":"Ji","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, School of Basic Medical Sciences and Clinical Pharmacy China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6730-8219","authenticated-orcid":false,"given":"Yu\u2010Wen","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Sir Run Run Hospital Nanjing Medical University  Nanjing China"},{"name":"School of Pharmacy Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375\u2010020\u201001072\u20106"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2022.0031"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0000000000000412"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.630942"},{"key":"e_1_2_11_6_1","unstructured":"FDA.Ibrutinib FDA label SUPPL\u201038. 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