Cardiovascular events and atherogenic lipid profile in chronic myeloid leukemia patients treated with nilotinib versus imatinib

Abstract

The aim of this study was to assess cardiotoxicity and potential adverse effects related to lipid metabolism during treatment with tyrosine kinase inhibitors (TKIs) imatinib and nilotinib in patients with chronic myeloid leukemia (CML). PATIENTS AND METHODS: Eighty-two consecutive patients with CML, who received nilotinib and/or imatinib in a single haemato-oncological Slovak center between years 2002-2018 were evaluated in a retrospective study. The mean age was 55.8 years (range 22-77 years). Median of follow-up was 61.3 months. RESULTS: A signifi cantly higher incidence of dyslipidemia, signifi cantly higher levels of potential risk markers of cardiovascular disease small dense LDL cholesterol (sdLDL-CH) and a signifi cant increase in total cholesterol were found in the patients during treatment with nilotinib in comparison to imatinib. Dyslipidemia led to drug therapy in 22 % of the patients in the nilotinib group. Fourteen percent of the patients in the nilotinib group had one or more cardiovascular events, including peripheral artery disease (10 %), myocardial infarction (4 %) and stroke (4 %). CONCLUSION: A higher risk of cardiovascular events and atherogenic dyslipidemia were associated with nilotinib therapy. Patients treated with TKI, especially nilotinib, require an early modifi cation of cardiovascular risk factors and a careful cardiologic surveillance so that antileukemic therapy with this highly effective agent could continue (Tab. 4, Fig. 3, Ref. 32).

Three tyrosine kinase inhibitors cause cardiotoxicity by inducing endoplasmic reticulum stress and inflammation in cardiomyocytes

“…Both TKIs cause hypertension in up to 47% of patients, which is probably due to inhibition of the VEGF signaling [ 4 ]. In another study, 14% of patients with nilotinib treatment have one or more cardiovascular events, including peripheral artery disease (10%) and myocardial infarction (4%) [ 5 ]. Ponatinib is associated with a significant incidence of arterial occlusion events (26%) [ 6 ] and other adverse cardiac events, including arrhythmia, hypertension, and myocardial infarction [ 7 ].…”

Coronary atherosclerosis and chemotherapy: From bench to bedside

“…Another study showed that 7.5% of patients treated with nilotinib developed acute coronary syndrome, among whom two patients had acute myocardial infarction and one patient died ( 34 ). In another single-center retrospective study that also demonstrated nilotinib-associated cardiovascular toxicity, Petrikova et al ( 35 ) evaluated cardiovascular events in 82 patients with CML who received nilotinib or imatinib. In the nilotinib group, 14% of patients had one or more cardiovascular events, with myocardial infarction accounting for 4% of all events ( 35 ).…”

“…In another single-center retrospective study that also demonstrated nilotinib-associated cardiovascular toxicity, Petrikova et al ( 35 ) evaluated cardiovascular events in 82 patients with CML who received nilotinib or imatinib. In the nilotinib group, 14% of patients had one or more cardiovascular events, with myocardial infarction accounting for 4% of all events ( 35 ). The effects of sunitinib and sorafenib on tumor-associated endothelial cells may also lead to the activation of systemic coagulation in patients with cancer, making them more susceptible to thromboembolism.…”