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Cardiovascular Events Associated With Use of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: A Population-Based Cohort Study
Department of Medicine, Division of Hematology, Karolinska University Hospital Solna, SE-17176 Stockholm, Sweden..
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-17177 Stockholm, Sweden..
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-17177 Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
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2016 (English)In: Annals of Internal Medicine, ISSN 0003-4819, E-ISSN 1539-3704, Vol. 165, no 3, 161-166 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2016. Vol. 165, no 3, 161-166 p.
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-302681DOI: 10.7326/M15-2306ISI: 000380583300004PubMedID: 27295519OAI: oai:DiVA.org:uu-302681DiVA: diva2:970917
Available from: 2016-09-15 Created: 2016-09-08 Last updated: 2016-09-15Bibliographically approved

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Höglund, MartinOlsson-Strömberg, Ulla
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