Should dasatinib (Sprycel) be continued or discontinued in a patient with heart failure?

Dasatinib Should Be Discontinued in Patients with Heart Failure

Dasatinib should be discontinued in patients with heart failure due to its known cardiovascular toxicity and potential to worsen cardiac function.

Cardiovascular Risks of Dasatinib

• Dasatinib can cause cardiac dysfunction as documented in the FDA drug label, with cardiac-related fluid retention occurring in 8.5% of patients 1
• Dasatinib is associated with significant cardiovascular toxicity including cardiac ischemic events, conduction system abnormalities, and peripheral arterial occlusive disease 1
• The European Society of Cardiology guidelines specifically recommend avoiding tyrosine kinase inhibitors like dasatinib in patients with severe (NYHA class III and IV) cardiac failure 2
• Patients with prior cardiac history and hypertension are at increased risk of developing complications while on dasatinib 2

Pulmonary Arterial Hypertension Risk

• Dasatinib may increase the risk of developing pulmonary arterial hypertension (PAH) which can occur at any time after initiation, including after more than 1 year of treatment 1
• In the DASISION study, pulmonary hypertension was reported in 5% of patients treated with dasatinib compared with <1% of patients treated with imatinib 2
• If pulmonary arterial hypertension is confirmed, dasatinib must be permanently discontinued according to FDA guidelines 1
• Multiple case reports demonstrate that dasatinib-induced PAH can lead to right heart failure but may be partially or completely reversible upon discontinuation 3, 4, 5

Fluid Retention and Pleural Effusion

• Dasatinib causes fluid retention in a significant percentage of patients, with Grade 3 or 4 fluid retention reported in 5-8% of patients 1
• Pleural effusion is a common adverse effect of dasatinib (28% in the DASISION study) and can worsen heart failure symptoms 2
• Fluid retention events may require management with diuretics or short courses of steroids, and severe pleural effusion may require thoracentesis and oxygen therapy 1
• Patients with heart failure are particularly vulnerable to fluid overload complications from dasatinib 2

Alternative Treatment Options

• Consider switching to an alternative tyrosine kinase inhibitor with a more favorable cardiovascular profile 2
• Imatinib has been associated with fewer cardiovascular complications compared to dasatinib in clinical trials 2
• Nilotinib is another alternative, though it has its own cardiovascular risk profile that should be considered 2
• The NCCN guidelines suggest that treatment interruption of dasatinib and reintroduction at a lower dose may be effective for patients with intolerance, but this approach is not recommended in heart failure 2

Monitoring Recommendations if Continuation is Absolutely Necessary

• If continuation of dasatinib is absolutely necessary (which is not recommended in heart failure), close monitoring of cardiac function with regular echocardiograms is essential 2
• Evaluate patients for signs and symptoms of underlying cardiopulmonary disease prior to initiating dasatinib and during treatment 1
• Monitor for symptoms of pleural effusion or other fluid retention, such as new or worsened dyspnea, pleuritic chest pain, or dry cough 1
• Regular assessment of pulmonary artery pressure through echocardiography should be performed 5

Conclusion

Dasatinib poses significant cardiovascular risks, particularly in patients with pre-existing heart failure. The evidence strongly supports discontinuation of dasatinib in patients with heart failure, with consideration of alternative TKIs that may have more favorable cardiovascular profiles. The potential for dasatinib to cause or exacerbate pulmonary hypertension, which can further compromise cardiac function, makes it particularly unsuitable for patients with heart failure.