Background. Tyrosine kinase inhibitors (TKIs) have shown long-term survival benefits in chronic myeloid leukemia (CML) patients. 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 CML patients 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 (TCRD) and National Health Insurance Research Database (NHIRD). 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 CML patients were included in our study. We found that the risk of VAEs in nilotinib users was significantly higher than that in imatinib users, with a hazard ratio (HR) of 3.13 (95% confidence interval (CI) 1.30-7.51), while 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. Conclusion. These findings can support clinicians in making treatment decisions and monitoring VAEs in CML patients in Taiwan. The Oncologist 2021;9999:• • Implications for Practice: Our study found that CML patients treated with nilotinib and dasatinib may exposed to higher risk of developing vascular adverse events compared to those who treated with imatinib. Thus, we suggest that CML patients 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 TKIs.

From October 2001 to October 2003, the authors reviewed all patients with chronic seizures taking antiepileptic drugs for more than 2 years with follow-up at the pediatric neurological clinic. They identified 31 patients who were using 3 or more drugs. Twenty-nine patients agreed to undergo a drug reduction and readjustment. The authors spent a mean period of 14.1 months to either purely reduce the numbers of drugs or introduce a new drug (rational polytherapy) plus removal of some drugs to achieve the end goal of a maximum of 2 or 3 drugs (if necessary). Seizure control in 96.6% of patients (28 of 29 patients) did not worsen after the readjustment and reduction of the antiepileptic drugs. Instead, 65.5% (19 of 29 patients) got better, and 37.9% (11 of 29) were seizure free. The number of antiepileptic drugs before and after adjusting was 3.6 (range, 3-6) to 1.9 (4 monotherapy, 22 duotheray, and 2 triple drugs). The most common combined therapies were sodium valproate/lamotrigine (n = 10) and carbamazepine/ topiramate (n = 5). Although the results could be possibly attributed to the spontaneous remission of the seizures, it was still shown that those patients were overtreated. Serial addition to 3 or more antiepileptic drugs is less likely to lead to seizure freedom for patients with difficult-to-treat epilepsy. On the contrary, polytherapy and some antiepileptic drugs could aggravate seizures. Certain combinations of antiepileptic drugs (rational polytherapy) offer better efficacy to control seizures.