Tyrosine kinase inhibitor use in chronic myeloid leukemia was associated with increased risks of arterial (RR 1.5; 95% CI 1.1-2.1) and venous (RR 2.0; 95% CI 1.2-3.3) vascular events.
Cohort (n=5,376)
Yes
Does the use of tyrosine kinase inhibitors increase the risk of arterial and venous vascular events in patients with chronic myeloid leukemia?
The use of tyrosine kinase inhibitors in patients with chronic myeloid leukemia is associated with a significantly increased risk of both arterial and venous vascular events compared to the general population.
Relative Risk: 1.5 (95% CI 1.1–2.1)
BACKGROUND: Tyrosine kinase inhibitors (TKIs) have increased survival dramatically for patients with chronic myeloid leukemia (CML), but continuous administration of these drugs may elicit long-term toxicity. OBJECTIVE: To investigate the incidence of vascular events in patients with CML treated with first- and second-generation TKIs. DESIGN: Retrospective cohort study using nationwide population-based registries. SETTING: Sweden. PATIENTS: All patients diagnosed with chronic-phase CML in Sweden from 2002 to 2012 and treated with a TKI, and 5 age- and sex-matched control individuals per patient. MEASUREMENTS: Relative risks, expressed as incidence rate ratios comparing patients with control individuals, were calculated. Events per 1000 person-years were assessed in interdrug comparisons. RESULTS: 896 patients, 94.4% with documented TKI treatment, were followed for a median of 4.2 years. There were 54 arterial and 20 venous events in the CML cohort, corresponding to relative risks of 1.5 (95% CI, 1.1 to 2.1) and 2.0 (CI, 1.2 to 3.3), respectively. The event rate for myocardial infarction was higher in patients treated with nilotinib or dasatinib (29 and 19 per 1000 person-years, respectively) than in those receiving imatinib (8 per 1000 person-years), although data are limited and the CIs were wide and overlapped. Among 31 patients treated with a TKI who had myocardial infarction, 26 (84%) had at least 1 major cardiac risk factor diagnosed before the event occurred. LIMITATIONS: Patients may have been exposed to multiple TKIs. Data on second- and third-generation TKIs were limited. CONCLUSION: An increased risk for arterial and venous vascular events was seen in patients with CML treated with a TKI. Further study is needed to determine whether the risk for myocardial infarction increases with second-generation drugs. PRIMARY FUNDING SOURCE: No external funding.
Dahlén et al. (2016) conducted a cohort in Chronic myeloid leukemia (n=5,376). Tyrosine kinase inhibitors vs. Age- and sex-matched control individuals was evaluated on Arterial events (RR 1.5, 95% CI 1.1-2.1). Tyrosine kinase inhibitor use in chronic myeloid leukemia was associated with increased risks of arterial (RR 1.5; 95% CI 1.1-2.1) and venous (RR 2.0; 95% CI 1.2-3.3) vascular events.