AUTHOR=Nunes Rafael Amorim Belo , Neves Precil Diego Miranda de Menezes , da Costa Leandro Menezes Alves , Bachour Philip , Cantarelli Marcelo José de Carvalho , Oliveira Gustavo Bernardes de Figueiredo , Avezum Jr. Álvaro 

TITLE=Five-year cardiovascular outcomes in patients with chronic myeloid leukemia treated with imatinib, dasatinib, or nilotinib: A cohort study using data from a large multinational collaborative network

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.888366

DOI=10.3389/fcvm.2023.888366

ISSN=2297-055X

ABSTRACT=Background
BCR-ABL tyrosine kinase inhibitors (TKI) have revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, concern has arisen about the cardiac safety profile of these drugs. 

Objectives
To compare long-term risks of adverse cardiovascular and cerebrovascular events (ACE), heart failure or left ventricular ejection fraction (LVEF) < 50% and venous thromboembolic events (VTE) in patients with CML treated with Bcr-ABL TKIs, using data from a large multinational network.

Methods
Patients aged ≥ 18 years with chronic myeloid leukemia treated with imatinib, dasatinib, or nilotinib without prior cardiovascular or cerebrovascular disease. We used propensity score matching to balance the cohorts. The 5-year cumulative incidences and hazard ratios were calculated. 

Results
We identified 3,722 patients with CML under treatment with imatinib (n = 1,906), dasatinib (n = 1,269) and nilotinib (n = 547).  Patients with imatinib compared to dasatinib showed a higher hazard ratio (HR) for ACE (HR 2,13, 95% IC 1.15-3.94, p= 0.016). Patients with imatinib presented a lower hazard ratio than nilotinib for ACE (HR 0.50, 95% IC 0.30-0.83, p= 0.0074). In relation to heart failure or LVEF < 50%, patients with imatinib had a higher hazard ratio than dasatinib (HR 9.41, 95% IC 1.22-72.17, p= 0.03), but no significant difference was observed between imatinib and nilotinib (HR 0.48, 95% IC 0,215-1.01, p= 0.064).

Conclusions	
In this retrospective study with a large number of patients with CML, those treated with nilotinib had a higher 5-year ratio of adverse cardiovascular and cerebrovascular events, while patients with dasatinib showed a lower ratio than patients with imatinib. The ratio of heart failure was higher in patients with imatinib than in patients with dasatinib, but not when compared to nilotinib.