Can bosutinib (Bosulif) worsen heart failure?

Bosutinib and Heart Failure: Cardiovascular Risk Assessment

Bosutinib can worsen pre-existing heart failure and is associated with cardiovascular toxicity, including cardiac failure and left ventricular dysfunction, particularly in patients with pre-existing cardiac conditions or risk factors. 1

Cardiovascular Risks of Bosutinib

Bosutinib (Bosulif) has documented cardiovascular effects as stated in the FDA label:

• Cardiac failure events occur more frequently in previously treated patients than in newly diagnosed chronic myeloid leukemia (CML) patients
• Higher risk in patients with advanced age or risk factors, including previous history of cardiac failure
• Cardiac ischemic events are more common in patients with coronary artery disease risk factors (diabetes, obesity, hypertension, vascular disorders)
• In a randomized study with newly diagnosed CML, cardiac failure occurred in 1.9% of patients treated with bosutinib 1

Comparison with Other Tyrosine Kinase Inhibitors (TKIs)

The National Comprehensive Cancer Network (NCCN) guidelines provide important context for TKI selection based on cardiovascular risk:

• Dasatinib or bosutinib may be preferred in patients with a history of arrhythmias, heart disease, pancreatitis, or hyperglycemia 2
• Nilotinib and ponatinib carry higher risks of arteriovascular events than bosutinib 2
• Imatinib may be preferred for older patients with comorbidities, especially cardiovascular comorbidities 2

Risk Factors for Cardiovascular Toxicity with Bosutinib

Patients at higher risk for bosutinib-related cardiac complications include those with:

• Previous history of cardiac failure
• Advanced age
• Coronary artery disease risk factors (diabetes, obesity, hypertension)
• Pre-existing cardiovascular disease 1

Monitoring Recommendations

For patients on bosutinib with heart failure or at risk:

• Monitor for signs and symptoms consistent with cardiac failure
• Perform baseline cardiac assessment before initiating therapy
• Regular cardiac monitoring during treatment
• Watch for symptoms such as shortness of breath, weight gain, chest pain, or swelling in extremities 1

Management of Cardiovascular Toxicity

If cardiovascular toxicity occurs:

1. Interrupt treatment if symptoms of heart failure develop or worsen
2. Dose reduce as clinically indicated
3. Discontinue bosutinib if necessary based on severity of cardiac symptoms 1

Special Considerations

• Fluid retention, including pericardial effusion and pleural effusion, can occur with bosutinib and may exacerbate heart failure symptoms 1
• Case reports have documented worsening pulmonary arterial hypertension and pleural effusions with bosutinib, particularly in patients previously treated with dasatinib 3
• The incidence of atrial fibrillation with bosutinib ranges from 0.34% to 5.1%, which can further complicate heart failure management 2

Practical Approach

For patients with pre-existing heart failure who require bosutinib:

1. Perform comprehensive cardiac evaluation before starting therapy
2. Consider alternative TKIs if appropriate (imatinib may be safer for cardiovascular risk)
3. Start with lower initial doses (200 mg) with gradual escalation to reduce toxicity 4
4. Monitor cardiac function regularly during treatment
5. Manage heart failure symptoms aggressively with standard medical therapy

Conclusion

Bosutinib should be used with caution in patients with pre-existing heart failure. Close monitoring and prompt intervention are essential to minimize cardiovascular morbidity and mortality in these patients.