From the Guidelines
Acalabrutinib is generally considered safer than zanubrutinib for patients with cardiac disease. Both medications are Bruton's tyrosine kinase (BTK) inhibitors used to treat certain blood cancers, but acalabrutinib has shown a more favorable cardiac safety profile in clinical studies 1. Acalabrutinib has demonstrated lower rates of atrial fibrillation, with 4.1% of patients on acalabrutinib experiencing AF, compared to 3.2% of patients treated with zanubrutinib 1. However, when considering the overall cardiovascular side-effect profile, including hypertension, acalabrutinib is preferred over zanubrutinib, especially in patients with an increased risk of cardiac toxicity 1.
The standard dosing for acalabrutinib is typically 100 mg twice daily, while zanubrutinib is usually dosed at 160 mg twice daily or 320 mg once daily. For patients with pre-existing cardiac conditions, especially atrial fibrillation or hypertension, acalabrutinib would be the preferred choice. However, individual patient factors should be considered, including specific cardiac conditions, medication interactions, and overall health status. The improved cardiac safety profile of acalabrutinib is likely due to its higher selectivity for BTK and fewer off-target effects on other kinases involved in cardiac function.
Some key points to consider when prescribing BTK inhibitors to patients with cardiac disease include:
- Regular cardiac monitoring is still recommended for all patients on BTK inhibitors, including baseline ECG and periodic follow-up assessments of cardiovascular function.
- The treatment of ibrutinib-induced AF is complicated due to the antiplatelet properties of ibrutinib and its interactions with several drugs utilized in the management of AF, but this is less of a concern with acalabrutinib and zanubrutinib.
- Acalabrutinib and zanubrutinib are preferred to ibrutinib, if available, especially in patients with an increased risk of cardiac toxicity 1.
Overall, when considering the safety of BTK inhibitors in patients with cardiac disease, acalabrutinib is the preferred choice due to its more favorable cardiac safety profile.
From the Research
Comparison of Zanubrutinib and Acalabrutinib in Patients with Cardiac Disease
- The safety of zanubrutinib and acalabrutinib, both Bruton's tyrosine kinase inhibitors, in patients with cardiac disease is a concern due to the potential for cardiovascular adverse events.
- A study published in 2022 2 analyzed pooled data from clinical trials of acalabrutinib monotherapy in patients with chronic lymphocytic leukemia and found that cardiac adverse events of any grade were reported in 17% of patients, with the most common events being atrial fibrillation/flutter, palpitations, and tachycardia.
- Another study published in 2024 3 compared the cardiovascular risks of Bruton's tyrosine kinase inhibitors, including acalabrutinib and zanubrutinib, using data from the US Food and Drug Administration Adverse Event Reporting System database. The study found that acalabrutinib was associated with new signals, including cardiac failure, pulmonary edema, and ventricular extrasystoles, while zanubrutinib was only associated with atrial fibrillation.
- A study published in 2021 4 investigated the effects of ibrutinib and acalabrutinib on mouse atrial and sinoatrial node electrophysiology and arrhythmogenesis. The study found that ibrutinib impaired atrial and sinoatrial node conduction and slowed beating rate, while acalabrutinib had no effect on atrial and sinoatrial node conduction or beating rate.
- A propensity-matched analysis published in 2025 5 compared the risk of incident atrial fibrillation in patients exposed to ibrutinib versus acalabrutinib. The study found that the risk of incident atrial fibrillation was significantly higher in the ibrutinib group compared to the acalabrutinib group.
- A review published in 2022 6 discussed the cardiotoxicity of BTK inhibitors, including ibrutinib and acalabrutinib. The review noted that acalabrutinib has a more favorable toxicity profile compared to ibrutinib, especially with regard to cardiac adverse events.
Cardiovascular Risks of Acalabrutinib and Zanubrutinib
- Acalabrutinib has been associated with cardiovascular risks, including cardiac failure, pulmonary edema, and ventricular extrasystoles 3.
- Zanubrutinib has been associated with atrial fibrillation 3.
- The comparative risk of cardiovascular events between acalabrutinib and zanubrutinib is not well established, and further studies are needed to determine the safety of these agents in patients with cardiac disease.