BACKGROUND: Tyrosine kinase inhibitors (TKIs) have shown long-term survival benefits in patients with chronic myeloid leukemia (CML). Nevertheless, significant concern has been raised regarding long-term TKI-associated vascular adverse events (VAEs). The objective of this retrospective cohort study was to investigate the incidence of VAEs in Taiwanese patients with CML treated with different TKIs (imatinib, nilotinib, and dasatinib) as well as potential risk factors.
METHODS: We conducted a retrospective cohort study using the Taiwan Cancer Registry Database and National Health Insurance Research Database. Adult patients diagnosed with CML from 2008 to 2016 were identified and categorized into three groups according to their first-line TKI treatment (imatinib, nilotinib, and dasatinib). Propensity score matching was performed to control for potential confounders. Cox regressions were used to estimate the hazard ratio (HR) of VAEs in different TKI groups.
RESULTS: In total, 1,111 patients with CML were included in our study. We found that the risk of VAEs in nilotinib users was significantly higher than that in imatinib users, with an HR of 3.13 (95% confidence interval (CI), 1.30-7.51), whereas dasatinib users also showed a nonsignificant trend for developing VAEs, with an HR of 1.71 (95% CI, 0.71-4.26). In multivariable logistic regression analysis, only nilotinib usage, older age, and history of cerebrovascular diseases were identified as significant risk factors. The annual incidence rate of VAEs was highest within the first year after the initiation of TKIs.
CONCLUSIONS: These findings can support clinicians in making treatment decisions and monitoring VAEs in patients with CML in Taiwan.
CONCLUSIONS: This study found that patients with chronic myeloid leukemia (CML) treated with nilotinib and dasatinib may be exposed to a higher risk of developing vascular adverse events (VAEs) compared with those treated with imatinib. Thus, this study suggests that patients with CML who are older or have a history of cerebrovascular diseases should be under close monitoring of VAEs, particularly within the first year after the initiation of tyrosine kinase inhibitors.

This study investigated the incidence rate and features of vascular adverse events (VAEs) in Japanese patients with chronic myeloid leukemia (CML) who were treated with tyrosine kinase inhibitors (TKIs). The analysis included 369 CML patients in the chronic or accelerated phases, selected from the CML Cooperative Study Group database; 25 events in 23 (6.2%) of these patients were VAEs. At the time of VAE incidence, nine patients were on treatment with imatinib, 12 with nilotinib, three with dasatinib, and one with bosutinib. VAE incidence comprised 13 cases of ischemic heart disease (IHD), eight of cerebral infarction (CI), and four of peripheral arterial occlusive disease (PAOD). IHD incidence rate in the study population was higher than that in the age-matched general population, particularly in nilotinib-treated patients, while CI incidence rate was almost equivalent. Compared with the Suita score, the SCORE chart and the Framingham score risk assessment tools detected more patients with high or very high risk of VAEs. In conclusion, incidence of IHD requires closer monitoring in nilotinib-treated patients. More detailed investigations for determining the most useful tool to predict VAE incidence and long-term analysis of therapy-related VAE cases are needed for improving safety during TKI therapy.