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Cardiovascular events associated with use of tyrosine kinase inhibitors in chronic myeloid leukemia

Dahlén, Torsten; Edgren, Gustaf; Lambe, Mats; Höglund, Martin; Björkholm, Magnus; Sandin, Fredrik; Själander, Anders; Richter, Johan LU ; Olsson-Strömberg, Ulla and Ohm, Lotta, et al. (2016) In Annals of Internal Medicine 165(3). p.161-166
Abstract

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 ageand sex-matched control individuals per patient. Measurements: Relative risks, expressed as incidence rate ratios comparing patients with control individuals, were calculated. Events per 1000... (More)

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 ageand 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.

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Annals of Internal Medicine
volume
165
issue
3
pages
6 pages
publisher
American College of Physicians
external identifiers
  • Scopus:84980347521
ISSN
0003-4819
DOI
10.7326/M15-2306
language
English
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yes
id
7eb2cb0a-190e-4eeb-8a0f-4f0018d4ab1c
date added to LUP
2016-08-25 16:17:21
date last changed
2016-11-08 15:05:35
@misc{7eb2cb0a-190e-4eeb-8a0f-4f0018d4ab1c,
  abstract     = {<p>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 ageand 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.</p>},
  author       = {Dahlén, Torsten and Edgren, Gustaf and Lambe, Mats and Höglund, Martin and Björkholm, Magnus and Sandin, Fredrik and Själander, Anders and Richter, Johan and Olsson-Strömberg, Ulla and Ohm, Lotta and Bäck, Magnus and Stenke, Leif},
  issn         = {0003-4819},
  language     = {eng},
  month        = {08},
  number       = {3},
  pages        = {161--166},
  publisher    = {ARRAY(0x95b93c0)},
  series       = {Annals of Internal Medicine},
  title        = {Cardiovascular events associated with use of tyrosine kinase inhibitors in chronic myeloid leukemia},
  url          = {http://dx.doi.org/10.7326/M15-2306},
  volume       = {165},
  year         = {2016},
}