{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T15:30:20Z","timestamp":1793719820556,"version":"4.6.1"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fixed\u2010duration combination of ibrutinib and venetoclax (IV) has emerged as a highly effective first\u2010line treatment for chronic lymphocytic leukemia (CLL). However, the cardiac safety profile of this regimen has not been comprehensively characterized. We conducted a systematic review and meta\u2010analysis to evaluate the incidence and relative risk of cardiac adverse events associated with frontline IV\u2010based therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed, Embase, and major hematology conference proceedings (2014\u20132025) were searched for prospective studies evaluating first\u2010line IV\u2010based regimens in CLL\/SLL. Two analyses were performed: (1) pooled incidence of cardiac events across prospective trials and (2) comparative meta\u2010analysis of randomized controlled trials (RCTs) comparing IV\u2010based therapy with chemoimmunotherapy (CIT). The primary outcome was summed cardio\u2010vascular events (SCE). Secondary outcomes included atrial fibrillation\/flutter (AF), hypertension (HTN), ventricular arrhythmias, and cardiac mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fourteen publications comprising 1522 patients were included in the pooled analysis, and four RCTs were included in the comparative analysis. The pooled incidence of SCE was 18.0% (95% CI 12.8\u201323.9), while grade\u2009\u2265\u20093 SCE occurred in 6.6% (95% CI 4.6\u20138.8). AF\/flutter occurred in 10.8% (95% CI 8.6\u201313.3), with grade\u2009\u2265\u20093 AF in 3.6% (95% CI 2.6\u20134.9). HTN was reported in 19.0% (95% CI 12.5\u201326.8), with grade\u2009\u2265\u20093 HTN in 8.3% (95% CI 5.6\u201311.4). Ventricular arrhythmias\/cardiac arrest and cardiac mortality were uncommon, occurring in 0.78% and 0.89% of patients, respectively. Compared with CIT, IV\u2010based therapy was associated with significantly higher risks of SCE (RR 3.61, 95% CI 2.32\u20135.62), grade\u2009\u2265\u20093 SCE (RR 6.86, 95% CI 3.05\u201315.43), AF (RR 5.50, 95% CI 2.68\u201310.10), grade\u2009\u2265\u20093 AF (RR 9.82, 95% CI 2.69\u201335.84), HTN (RR 3.73, 95% CI 2.14\u20136.50), and grade\u2009\u2265\u20093 HTN (RR 4.91, 95% CI 2.06\u201311.67).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Frontline IV\u2010based therapy is associated with a clinically meaningful increase in cardiac toxicity, particularly AF and HTN, compared with CIT. Nevertheless, ventricular arrhythmias and cardiac mortality remain rare. Careful cardiovascular risk assessment and monitoring should accompany the use of IV\u2010based regimens in clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ejh.70300","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:02:44Z","timestamp":1787821364000},"page":"1612-1621","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiac Adverse Events in Patients With Chronic Lymphocytic Leukemia Treated With First\u2010Line Ibrutinib\u2013Venetoclax"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0393-2615","authenticated-orcid":false,"given":"Liron","family":"Hofstetter","sequence":"first","affiliation":[{"name":"Institute of Hematology, Davidoff Cancer Center Rabin Medical Centre  Petah Tikva Israel"},{"name":"The Gray Faculty of Medical and Health Sciences Tel Aviv University  Tel Aviv 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