What is the impact of Chronic Lymphocytic Leukemia (CLL) on cardiovascular health?

From the Guidelines

Chronic Lymphocytic Leukemia (CLL) has a significant impact on cardiovascular health, particularly due to the increased risk of atrial fibrillation (AF) associated with certain treatments, such as ibrutinib.

Key Points

• The risk of AF with ibrutinib is estimated to be between 3-16% [ 1 ], depending on the patient population and length of follow-up.
• Newer BTK inhibitors, such as acalabrutinib and zanubrutinib, have a lower incidence of AF compared to ibrutinib, with rates of 4.1% and 3.2%, respectively [ 1 ].
• The development of AF in patients with CLL is associated with an increased risk of mortality and serious complications, including ischemic stroke and heart failure [ 1 ].
• Cardiac assessment is crucial when planning to use a BTK inhibitor, such as ibrutinib, particularly in older patients with cardiac comorbidities [ 1 ].
• The treatment of ibrutinib-induced AF can be complicated due to the antiplatelet properties of ibrutinib and potential interactions with oral anticoagulants and other medications used to manage AF [ 1 ].
• Pre-treatment evaluation should include assessment of patient-related factors, such as comorbidities, particularly cardiac assessment, when choosing a treatment for CLL [ 1 ].

From the Research

Impact of Chronic Lymphocytic Leukemia (CLL) on Cardiovascular Health

• CLL patients are at a higher risk of developing cardiovascular disease (CVD) due to various factors, including monocytosis and chronic inflammation 2
• The use of Bruton tyrosine kinase (BTK) inhibitors, such as ibrutinib and acalabrutinib, in the treatment of CLL has been associated with an increased risk of cardiovascular adverse events, including atrial fibrillation, hypertension, and bleeding 3, 4, 5, 6
• Acalabrutinib has been shown to have a better cardiovascular safety profile compared to ibrutinib, with lower risks of atrial flutter or fibrillation, new-onset arterial hypertension, and sepsis 3
• Hypertension is a common toxicity in patients with CLL who receive ibrutinib, but it is manageable in most patients 4
• Older age, male sex, tobacco use, and chronic kidney disease have been identified as risk factors for ibrutinib-related hypertension 4
• The incidence of cardiovascular and bleeding events is high in patients with CLL treated with ibrutinib, and treatment discontinuation and dose reduction are common due to toxicity 5
• Novel agents used in the treatment of CLL, including ibrutinib, acalabrutinib, venetoclax, and idelalisib, have been associated with various cardiovascular adverse events, highlighting the need for robust cardiovascular surveillance after initiation of treatment 6

Cardiovascular Adverse Events Associated with CLL Treatment

• Atrial fibrillation is a common cardiovascular adverse event associated with ibrutinib treatment, with a frequency of 41.5% 6
• Hypertension is a significant concern in patients with CLL treated with ibrutinib, with a reported frequency of 25.6% in the acalabrutinib group and 11.8% in the venetoclax group 6
• Bleeding events are common in patients with CLL treated with ibrutinib, with a reported frequency of 66% 5
• Heart failure and myocardial infarction have been reported in patients with CLL treated with novel agents, including idelalisib and acalabrutinib 6