Cardiovascular events in patients with chronic myeloid leukaemia treated with tyrosine kinase inhibitors in Taiwan: a nationwide population-based study

Author:

Yang Yu-Chien12,Huang Ru-Yu3,Tsai Hui-Jen345,Li Po-Chih1,Yang Yi-Hsin13,Hsieh Kun-Pin16ORCID

Affiliation:

1. School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Sanmin Dist., Kaohsiung City 80708, Taiwan

2. Department of Pharmacy, E-Da Hospital, No. 1, Yida Rd., Yanchao Dist., Kaohsiung City 824005, Taiwan

3. National Institute of Cancer Research, National Health Research Institutes, No. 367, Sheng-Li Road, North District, Tainan 70456, Taiwan

4. Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd., Sanmin District, Kaohsiung City 80756, Taiwan

5. Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No. 138, Sheng-Li Road, North District, Tainan 70456, Taiwan

6. Department of Pharmacy, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd., Sanmin District, Kaohsiung City 80756, Taiwan

Abstract

Abstract Aims New-generation breakpoint cluster region-Abelson tyrosine kinase inhibitors (TKIs) have a higher incidence of cardiovascular events than imatinib in patients with chronic myeloid leukaemia (CML). However, this knowledge is insufficiently proven. Hence, this study aimed to explore the association between cardiovascular events and TKIs in patients with CML. Methods and results This retrospective population-based cohort study enrolled first-time users of imatinib, dasatinib, and nilotinib between 1 January 2007 and 31 December 2016. Arterial thromboembolic events (ATEs) were the primary outcome, while other cardiovascular-related events were the secondary outcomes. The event rates were estimated using Kaplan–Meier estimates, and the hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. Additionally, the competing risk was adjusted using the Fine and Gray competing risk model. We included 1207 patients. Nilotinib had a significantly higher ATE risk (subdistribution HR = 4.92, 95% CI = 1.68–14.36) than imatinib. Conversely, no difference was found for other cardiovascular-related events. Risks of ATE and other cardiovascular-related events were similar between dasatinib and imatinib and between nilotinib and dasatinib. The risk of ATE hospitalization consistently increased throughout the main analyses and sensitivity analyses. Conclusion Nilotinib-treated patients had a significantly higher risk of developing ATE than imatinib-treated patients. However, the risks of ATE and other cardiovascular-related events were not significantly different between dasatinib and imatinib.

Funder

National Health Research Institutes in Taiwan

Publisher

Oxford University Press (OUP)

Subject

Cardiology and Cardiovascular Medicine,Epidemiology

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