Key result
Ibrutinib linked to sudden cardiac death rate of ~800 per 100,000 patient-years in CLL.
Why the study?
The incidence and clinical features of sudden cardiac death and asymptomatic arrhythmias in chronic lymphocytic leukemia patients treated with ibrutinib remain ill defined.
Does ibrutinib increase the risk of sudden cardiac death and asymptomatic arrhythmias in patients with chronic lymphocytic leukemia?
Cohort (n=131)
No
Does ibrutinib increase the risk of sudden cardiac death and asymptomatic arrhythmias in patients with chronic lymphocytic leukemia?
Effect estimate: Incidence rate 801 per 100,000 patient-years
Ibrutinib is associated with an elevated risk of sudden cardiac death and asymptomatic arrhythmias, highlighting the need for proactive cardiac screening and monitoring in this population.
May support arrhythmia screening in ibrutinib-treated CLL; leaves open whether it reduces sudden death.
BACKGROUND: Ibrutinib (IBR) is a first-in-class Bruton's tyrosine kinase inhibitor (BTKi) approved in multiple hematologic conditions for indefinite use until disease progression or toxicity. Hypertension and atrial fibrillation are well-recognized cardiac complications of BTKi; more recently, heart failure, additional arrhythmias, and sudden cardiac death (SCD) have been attributed to IBR. Next-generation covalent BTKi are also associated with cardiovascular complications, including SCD, albeit to a lesser degree. OBJECTIVE: The incidence and clinical features of patients experiencing SCD and asymptomatic arrhythmias on IBR remain ill defined. We aimed to characterize the incidence of SCD and asymptomatic arrhythmias on IBR. METHODS: We report (1) a retrospective cohort analysis of 131 patients with a median of 66.5 months on IBR using available cardiac testing, genetic sequencing, and autopsy review and (2) a cross-sectional cardiac analysis of 21 asymptomatic patients on IBR including ambulatory electrocardiogram, stress tests, and transthoracic echocardiograms. RESULTS: The incidence of SCD in patients on IBR (n = 5) was 801 per 100,000 patient-years, approximately 2-4× higher than the general population. All patients with SCD on IBR had at least 1 cardiac risk factor. Autopsies conducted in 3 of 5 patients with SCD did not reveal acute pathologic processes, but did demonstrate evolving cardiac pathology. Cardiovascular testing in asymptomatic patients on IBR revealed previously unknown clinically significant arrhythmias in 4 patients (19%), leading to precautionary IBR discontinuation in 2 patients. CONCLUSION: IBR increases the risk of SCD among patients with cardiac risk factors. Stress and ambulatory electrocardiogram on IBR identified asymptomatic arrhythmias altering clinical management in 19% of patients. These data highlight the need for risk-mitigation strategies for patients starting or receiving IBR, possibly extending to other BTKis.
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Tomasulo et al. (2025) conducted a cohort in Chronic lymphocytic leukemia (n=131). Ibrutinib was evaluated on Incidence of sudden cardiac death (Incidence rate 801 per 100,000 patient-years). Ibrutinib exposure in patients with chronic lymphocytic leukemia was associated with a sudden cardiac death incidence of 801 per 100,000 patient-years, and screening revealed actionable asymptomatic arrhythmias in 19% of patients.
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