Objective: To identify factors that should be taken into account for the assessment of the necessity the cardiovascular (CV) risk reduction for chronic myeloid leukemia (CML) patients treated with BCR-ABL1 tyrosine kinase inhibitors (TKIs) in the decision making for strategy prevention.
Case report: CV risk reduction is an important consideration in patients with CML based on the necessity to improve prognosis in such a group of patients. The success and high effectiveness of TKIs have increased the focus on survivorship and late toxicity include CV toxicity in CML patients. Survivorship in CML patients depends on CV disease prevention, given its prevalence in the general population. The separate clinical guidelines for CML patients treated with TKIs for CV risk reduction are absent in clinical practice.
Methodology: We observed clinical trials expected TKIs effectiveness and toxicity (we especially focused on cardiotoxicity and hepatotoxicity), clinical guidelines on CV disease prevention for the general population. We also analyzed TKIs and HMG-CoA reductase inhibitors biotransformation, drug-drug interaction TKIs and HMG-CoA reductase inhibitors.
Results: TKIs demonstrated high effectiveness in CML patients based on the published clinical trials. Nilotinib and ponatinib have been linked to the development of vascular occlusive events, CV disease. Type 2 diabetes mellitus development can be associated with nilotinib treatment and as a result, could enhance CV disease. Dasatinib has been associated with pleural/pericardial effusions and pulmonary hypertension. Dasatinib based on clinical trial data is the most liver safe TKI, bosutinib, nilotinib, ponatinib have higher risks of hepatotoxicity in CML patients (ENESTnd trial, BELA Trial, DASISION trial, PACE study). The individual CV risk of the patient and the necessity of CV risk reduction should be based on the personal scores assessment with the cardiac risk score calculator, ASCVD algorithm based on the clinical guidelines on CV disease prevention for the general population. TKIs for CML treatment is the group of drugs that required liver biotransformation through CYP 3A4 cytochrome enzyme and are the inhibitors of CYP 3A4. Atorvastatin and simvastatin are required liver biotransformation with the CYP 3A4. Rosuvastatin and pravastatin are not required CYP 3A4 for their biotransformation. As a result, if atorvastatin or simvastatin are use with TKIs for CV risk reduction the HMG-CoA reductase inhibitors exposure increase and it should be taken into account in patients with abnormal liver tests due to TKIs using. Rosuvastatin or pravastatin exposure does not change due to simultaneous treatment with TKIs and could be a beneficial role for CV disease prevention.
Conclusion: The decision for the necessity of the CV risk reduction for CML patients treated with TKIs through strategy prevention should be based on the assessment the next factors: individual CV risk of the patient and the necessity of CV risk reduction, liver function, the metabolism peculiarities of TKIs using for CML treatment, the metabolism peculiarities of the HMG-CoA reductase inhibitor potential recommended for CV risk reduction, drug–drug interactions TKI and HMG-CoA reductase inhibitor.
