TY - JOUR
T1 - Association of Nilotinib With Cardiovascular Diseases in Patients With Chronic Myelogenous Leukemia
T2 - A National Population-Based Cohort Study
AU - Huang, Cih En
AU - Lee, Kuan Der
AU - Chang, Jung Jung
AU - Tzeng, Huey En
AU - Huang, Shih Hao
AU - Yu, Lennex Hsueh Lin
AU - Chen, Min Chi
N1 - © The Author(s) 2023. Published by Oxford University Press.
PY - 2024/1/5
Y1 - 2024/1/5
N2 - BACKGROUND: Tyrosine kinase inhibitor (TKI) treatment has been identified to be a risk factor for metabolic syndrome and cardiovascular diseases (CVDs) in patients diagnosed with chronic myeloid leukemia (CML). However, the specific contribution of post-TKI metabolic syndrome and the individual TKIs, including imatinib, nilotinib, and dasatinib, contribute to the development of CVDs remains unclear.METHODS: We conducted a nationwide database to investigate the incidence of post-TKI metabolic syndrome, including diabetes, hyperlipidemia, and hypertension, as well as their association with CVDs. To compare the risk of post-TKI comorbidities and CVDs among TKIs, we utilized the incidence rate ratio (IRR), and subdistribution hazard ratio (SHR) calculated from multiple Fine-Gray models.RESULTS: A total of 1211 patients without diabetes, 1235 patients without hyperlipidemia, and 1074 patients without hypertension were enrolled in the study. The incidence rate of post-TKI diabetes and hyperlipidemia was the highest in patients treated with nilotinib compared to imatinib and dasatinib (IRRs ≥ 3.15, Ps ≤ .047). After adjusting for confounders, nilotinib remained a significant risk factor for post-TKI diabetes and hyperlipidemia at an SHR of 3.83 (P < .001) and 5.15 (P < .001), respectively. Regarding the occurrence of CVDs, patients treated with nilotinib were more likely to develop CVDs than those treated with imatinib in non-hyperlipidemic group (IRR = 3.21, P = .020). Pre-existing and post-TKI hyperlipidemia were found to have a stronger association with CVDs, with SHR values of 5.81 (P = .034) and 13.21 (P = .001), respectively.CONCLUSION: The findings of this study indicate that nilotinib treatment is associated with increased risks of diabetes and hyperlipidemia, with hyperlipidemia being the most significant risk for CVDs. Therefore, we recommend that CML patients receiving nilotinib should undergo screening for diabetes and hyperlipidemia prior to initiating TKI treatment. Additionally, regular monitoring of lipid profiles during TKI therapy and implementing effective management strategies to control hyperlipidemia are crucial.
AB - BACKGROUND: Tyrosine kinase inhibitor (TKI) treatment has been identified to be a risk factor for metabolic syndrome and cardiovascular diseases (CVDs) in patients diagnosed with chronic myeloid leukemia (CML). However, the specific contribution of post-TKI metabolic syndrome and the individual TKIs, including imatinib, nilotinib, and dasatinib, contribute to the development of CVDs remains unclear.METHODS: We conducted a nationwide database to investigate the incidence of post-TKI metabolic syndrome, including diabetes, hyperlipidemia, and hypertension, as well as their association with CVDs. To compare the risk of post-TKI comorbidities and CVDs among TKIs, we utilized the incidence rate ratio (IRR), and subdistribution hazard ratio (SHR) calculated from multiple Fine-Gray models.RESULTS: A total of 1211 patients without diabetes, 1235 patients without hyperlipidemia, and 1074 patients without hypertension were enrolled in the study. The incidence rate of post-TKI diabetes and hyperlipidemia was the highest in patients treated with nilotinib compared to imatinib and dasatinib (IRRs ≥ 3.15, Ps ≤ .047). After adjusting for confounders, nilotinib remained a significant risk factor for post-TKI diabetes and hyperlipidemia at an SHR of 3.83 (P < .001) and 5.15 (P < .001), respectively. Regarding the occurrence of CVDs, patients treated with nilotinib were more likely to develop CVDs than those treated with imatinib in non-hyperlipidemic group (IRR = 3.21, P = .020). Pre-existing and post-TKI hyperlipidemia were found to have a stronger association with CVDs, with SHR values of 5.81 (P = .034) and 13.21 (P = .001), respectively.CONCLUSION: The findings of this study indicate that nilotinib treatment is associated with increased risks of diabetes and hyperlipidemia, with hyperlipidemia being the most significant risk for CVDs. Therefore, we recommend that CML patients receiving nilotinib should undergo screening for diabetes and hyperlipidemia prior to initiating TKI treatment. Additionally, regular monitoring of lipid profiles during TKI therapy and implementing effective management strategies to control hyperlipidemia are crucial.
KW - cardiovascular diseases
KW - chronic myeloid leukemia
KW - diabetes
KW - hyperlipidemia
KW - nilotinib
KW - Dasatinib
KW - Diabetes Mellitus/chemically induced
KW - Humans
KW - Cardiovascular Diseases/chemically induced
KW - Metabolic Syndrome/chemically induced
KW - Hypertension/chemically induced
KW - Imatinib Mesylate
KW - Protein Kinase Inhibitors/adverse effects
KW - Pyrimidines/adverse effects
KW - Hyperlipidemias/chemically induced
KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complications
KW - Cohort Studies
UR - http://www.scopus.com/inward/record.url?scp=85181761024&partnerID=8YFLogxK
U2 - 10.1093/oncolo/oyad225
DO - 10.1093/oncolo/oyad225
M3 - 文章
C2 - 37561957
AN - SCOPUS:85181761024
SN - 1083-7159
VL - 29
SP - E81-E89
JO - Oncologist
JF - Oncologist
IS - 1
ER -
