What are the cardiology concerns for patients taking Brukinsa (zanubrutinib)?

Cardiology Concerns for Patients Taking Brukinsa (Zanubrutinib)

Brukinsa (zanubrutinib) is associated with significant cardiac adverse events, particularly atrial fibrillation and cardiac arrhythmias, though at lower rates compared to first-generation BTK inhibitors like ibrutinib. Careful cardiac monitoring and management are essential for patients receiving this medication.

Primary Cardiac Concerns

1. Cardiac Arrhythmias

• Atrial fibrillation and atrial flutter occur in 4.4% of patients treated with Brukinsa, with Grade 3 or higher cases in 1.9% of patients 1
• Ventricular arrhythmias (Grade 3 or higher) reported in 0.3% of patients 1
• Patients with cardiac risk factors, hypertension, and acute infections are at increased risk for arrhythmias 1

2. Hemorrhage

• Fatal and serious hemorrhage has occurred in patients treated with Brukinsa 1
• Grade 3 or higher hemorrhage including intracranial and gastrointestinal hemorrhage occurs in 3.8% of patients 1
• Bleeding of any grade (excluding purpura and petechiae) occurs in 32% of patients 1
• Risk is higher with concomitant antiplatelet or anticoagulant medications 1

3. Hypertension

• Hypertension has been reported with Brukinsa, though at lower rates compared to first-generation BTK inhibitors 2
• Hypertensive urgency has been reported in patients with pre-existing hypertension 3

Monitoring Recommendations

Baseline Assessment

• Complete cardiac history and risk factor assessment
• 12-lead ECG to determine pre-existing cardiac conduction abnormalities 3
• Echocardiography to assess baseline cardiac function 3
• Consider cardiac biomarkers (troponin, BNP or NT-proBNP) 3

Ongoing Monitoring

• Regular monitoring for signs and symptoms of cardiac arrhythmias (palpitations, dizziness, syncope, dyspnea, chest discomfort) 1
• ECG monitoring, particularly in patients with risk factors for cardiac events
• Blood pressure monitoring at each clinical visit

Risk Stratification

High-Risk Patients

Patients with the following conditions require more careful monitoring:

• Pre-existing cardiac disease, especially atrial fibrillation
• Hypertension
• Concomitant use of anticoagulants or antiplatelet medications
• History of bleeding disorders
• Elderly patients

Contraindications

Brukinsa is contraindicated in patients with:

• Mobitz type II second-degree or third-degree atrioventricular block
• Sick sinus syndrome
• Sino-atrial block (unless patient has functioning pacemaker) 3

Management of Cardiac Events

Atrial Fibrillation/Flutter

• For new-onset atrial fibrillation, consider cardiology consultation
• Manage according to standard atrial fibrillation protocols
• Consider dose adjustment or interruption of Brukinsa if severe or symptomatic 1
• Evaluate risks and benefits of continuing Brukinsa

Bleeding Events

• Discontinue Brukinsa if intracranial hemorrhage of any grade occurs 1
• Consider withholding Brukinsa for 3-7 days before and after surgery depending on bleeding risk 1
• Monitor for signs and symptoms of bleeding

Hypertension

• Optimize blood pressure control before starting Brukinsa
• Treat hypertension according to standard guidelines
• Consider alternative therapy if hypertension becomes uncontrollable 3

Comparison with Other BTK Inhibitors

Brukinsa shows improved cardiac safety profile compared to first-generation BTK inhibitors:

• Lower incidence of atrial fibrillation/flutter compared to ibrutinib (6.1% vs 15.6%) 2
• Lower exposure-adjusted incidence rates for symptomatic ventricular arrhythmia (0.02 vs 0.06 persons per 100 person-months) 2
• Fewer discontinuations and deaths due to cardiac disorders compared to ibrutinib 2

Key Considerations for Specific Patient Populations

• Patients with pre-existing atrial fibrillation: Consider alternative therapy if requiring anticoagulation 3
• Patients on anticoagulants: Higher risk of bleeding; careful monitoring required 1
• Patients with multiple cardiovascular risk factors: More intensive monitoring recommended
• Elderly patients: May be at higher risk for cardiac events; consider more frequent monitoring

Common Pitfalls and Caveats

1. Failure to perform adequate baseline cardiac assessment before initiating therapy
2. Overlooking drug interactions that may increase cardiac risk
3. Delayed recognition of cardiac symptoms due to attribution to other causes
4. Inadequate monitoring of high-risk patients
5. Abrupt discontinuation of Brukinsa without planning for transition to alternative therapy, as disease progression may accelerate when BTK inhibitors are stopped 3

By understanding these cardiac concerns and implementing appropriate monitoring and management strategies, clinicians can optimize the safety profile of Brukinsa while maintaining its therapeutic efficacy in patients with B-cell malignancies.