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

• Published in: Annals of internal medicine Vol. 165; no. 3; p. 161
• Main Authors: Dahlén, Torsten, Edgren, Gustaf, Lambe, Mats, Höglund, Martin, Björkholm, Magnus, Sandin, Fredrik, Själander, Anders, Richter, Johan, Olsson-Strömberg, Ulla, Ohm, Lotta, Bäck, Magnus, Stenke, Leif
• Format: Journal Article
• Language: English
• Published: United States 02.08.2016
• Subjects: Antineoplastic Agents - adverse effects; Cardiovascular Diseases - chemically induced; Female; Humans; Leukemia, Myeloid, Chronic-Phase - drug therapy; Male; Middle Aged; Myocardial Infarction - chemically induced; Protein-Tyrosine Kinases - adverse effects; Protein-Tyrosine Kinases - antagonists & inhibitors; Retrospective Studies; Risk Factors; Venous Thromboembolism - chemically induced
• ISSN: 1539-3704
• DOI: 10.7326/M15-2306

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.