Medline ® Abstract for Reference 95
of 'Clinical use of tyrosine kinase inhibitors for chronic myeloid leukemia'
Cardiovascular Events Associated With Use of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: A Population-Based Cohort Study.
Dahlén T, Edgren G, Lambe M, Höglund M, Björkholm M, Sandin F, Själander A, Richter J, Olsson-Strömberg U, Ohm L, Bäck M, Stenke L, Swedish CML Group and the Swedish CML Register Group
Ann Intern Med. 2016;165(3):161. Epub 2016 Jun 14.
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.
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.