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

Eur J Prev Cardiol. 2022 Jul 20;29(9):1312-1321. doi: 10.1093/eurjpc/zwab043.

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.

Keywords: Adverse events; Cardiovascular diseases; Chronic myeloid leukaemia; Tyrosine kinase inhibitors.

MeSH terms

  • Cardiovascular Diseases* / chemically induced
  • Cardiovascular Diseases* / diagnosis
  • Cardiovascular Diseases* / epidemiology
  • Cohort Studies
  • Dasatinib / adverse effects
  • Humans
  • Imatinib Mesylate / adverse effects
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / diagnosis
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / epidemiology
  • Protein Kinase Inhibitors / adverse effects
  • Retrospective Studies
  • Taiwan / epidemiology

Substances

  • Protein Kinase Inhibitors
  • Imatinib Mesylate
  • Dasatinib