Cardiovascular Events Associated With Use of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: A Population-Based Cohort Study.
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.



To investigate the incidence of vascular events in patients with CML treated with first- and second-generation TKIs.



Retrospective cohort study using nationwide population-based registries.



Sweden.



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.



Relative risks, expressed as incidence rate ratios comparing patients with control individuals, were calculated. Events per 1000 person-years were assessed in interdrug comparisons.



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.



Patients may have been exposed to multiple TKIs. Data on second- and third-generation TKIs were limited.



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.



No external funding.
Torsten
T
Dahlén
Gustaf
G
Edgren
Mats
M
Lambe
Martin
M
Höglund
Magnus
M
Björkholm
Fredrik
F
Sandin
Anders
A
Själander
Johan
J
Richter
Ulla
U
Olsson-Strömberg
Lotta
L
Ohm
Magnus
M
Bäck
Leif
L
Stenke
D000970:Antineoplastic Agents / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D005260:Female; D006801:Humans; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced; D011505:Protein-Tyrosine Kinases / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000139:chemically induced
D000970:Antineoplastic Agents; D011505:Protein-Tyrosine Kinases