Ibrutinib and Cardiovascular Risk in Patients With Chronic Lymphocytic Leukemia

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In a Canadian population-based cohort study reported in the Journal of Clinical Oncology, Abdel-Qadir et al found that ibrutinib treatment for chronic lymphocytic leukemia (CLL) is associated with increased risks of atrial fibrillation, bleeding, and heart failure, but not ischemic stroke or acute myocardial infarction.

As stated by the investigators, “Ibrutinib reduces mortality in CLL. It increases the risk of atrial fibrillation and bleeding and there are concerns about heart failure and central nervous system ischemic events. The magnitude of these risks remains poorly quantified.”

Study Details

The study included data on 778 patients who received ibrutinib for treatment of CLL diagnosed in Ontario between 2007 and 2019. Ibrutinib-treated patients were paired with 778 patients who received chemotherapy without ibrutinib matched for prior atrial fibrillation, age ≥ 66 years, anticoagulant exposure, and propensity for receiving ibrutinib.

Key Findings

The 3-year incidence of atrial fibrillation–related health-care contact was 22.7% (95% confidence interval [CI] = 19.0%–26.6%) in ibrutinib-treated patients vs 11.7% (95% CI = 9.0%–14.8%) in controls (cause-specific hazard ratio [HR] = 2.04, 95% CI = 1.55–2.68, P < .001). 

Ibrutinib is associated with higher risk of atrial fibrillation, bleeding, and heart failure, but not acute myocardial infarction or stroke.
— Abdel-Qadir et al

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The 3-year risk of hospital-diagnosed bleeding was 8.8% (95% CI = 6.5%–11.7%) in ibrutinib-treated patients and 3.1% (95% CI = 1.9%–4.6%) in controls (cause-specific HR = 2.49, 95% CI = 1.56–3.99, P < .001). Although patients had similar rates of anticoagulant use at baseline, ibrutinib-treated patients were more likely to start anticoagulation after the index date (3-year cumulative incidence of anticoagulation = 23.5% vs 18.4%, P = .002). In analysis adjusting for anticoagulation as a time-varying covariate, ibrutinib use remained significantly associated with bleeding risk (cause-specific HR = 2.58, 95% CI = 1.76–3.78).

The 3-year risk of heart failure was 7.7% (95% CI = 5.4%–10.6%) in ibrutinib-treated patients vs 3.6% (95% CI = 2.2%–5.4%) in controls (cause-specific HR = 1.73, 95% CI = 1.02–2.93, P = .04).

Ischemic strokes and acute myocardial infarctions were infrequent and had comparable incidence in ibrutinib-treated patients vs controls; cause-specific hazard ratios were 0.89 (95% CI = 0.34–2.29, P = .80) for ischemic stroke and 1.23 (95% CI = 0.58–2.64, P = .59) for acute myocardial infarction. Among 1,064 patients aged ≥ 66 years who were not receiving anticoagulants at baseline, the 3-year cumulative incidence of ischemic stroke was 1.6% (95% CI = 0.6%–3.7%) in ibrutinib-treated patients vs 2.1% (95% CI = 0.9%–4.2%) in controls (P = .60), and the cumulative incidence of acute myocardial infarction was 2.1% (95% CI = 1.0%–3.9%) vs 1.2% (95% CI = 0.4%–2.6%, P = .06).

The investigators concluded, “Ibrutinib is associated with higher risk of atrial fibrillation, bleeding, and heart failure, but not acute myocardial infarction or stroke.”

Husam Abdel-Qadir, MD, PhD, of the Division of Cardiology, Women’s College Hospital, University of Toronto, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.