title: Risk of arterial and venous occlusive events in chronic myeloid leukemia patients treated with new generation BCR-ABL tyrosine kinase inhibitors: a systematic review and meta-analysis.
abstract: BACKGROUND
  A previous meta-analysis demonstrated that 3 of the new-generation BCR-ABL tyrosine kinase inhibitors (TKIs) (dasatinib, nilotinib and ponatinib) are associated with an increased risk of vascular occlusive events in patients with Ph+ chronic myeloid leukemia compared with imatinib. This meta-analysis of randomized controlled trials aims at assessing these risks separately.
  
  
  METHODS
  The literature search was performed by two independent reviewers following the previous protocol (PROSPERO 2014:CRD42014014147). A random-effects model and a fixed-effect model were used according to the characteristics of the included studies. Peto odds ratios with 95%CI were computed.
  
  
  RESULTS
  Overall, 4.78% of patients developed arterial occlusive events with new generation TKIs compared with 0.96% with imatinib. Ponatinib (ORPETO:3.26; 95%CI:1.12 to 9.50), nilotinib (ORPETO: 3.69; 95%CI:2.29 to 5.95) and dasatinib (ORPETO:3.32; 95%CI:1.37 to 8.01) are all associated with a higher risk of arterial occlusive events than imatinib. Venous occlusive events occur in 0.72% of patients treated with new generation TKIs and in 0.27% of imatinib-treated patients. Overall, a trend toward an increase of the rate of venous occlusive events with new-generation TKIs (ORPETO:2.17; 95%CI:0.90 to 5.25) was highlighted but stratifications by treatment gave nonsignificant results.
  
  
  CONCLUSIONS
  Vascular occlusive events associated with new-generation BCR-ABL TKIs are driven by arterial occlusive events.
authors.affiliation: a Department of Pharmacy , University of Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) , Namur , Belgium.|b Haematology Laboratory , Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) , Yvoir , Belgium.
authors.forename: Hélène
authors.initials: H
authors.lastname: Haguet
authors.affiliation: a Department of Pharmacy , University of Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) , Namur , Belgium.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Douxfils
authors.affiliation: b Haematology Laboratory , Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) , Yvoir , Belgium.
authors.forename: François
authors.initials: F
authors.lastname: Mullier
authors.affiliation: a Department of Pharmacy , University of Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) , Namur , Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Chatelain
authors.affiliation: c Department of Haematology , Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) , Yvoir , Belgium.
authors.forename: Carlos
authors.initials: C
authors.lastname: Graux
authors.affiliation: a Department of Pharmacy , University of Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) , Namur , Belgium.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dogné
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000069439:Dasatinib / Q000009:adverse effects / Q000627:therapeutic use; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors; D006801:Humans; D000068877:Imatinib Mesylate / Q000009:adverse effects / Q000627:therapeutic use; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011724:Pyridazines / Q000009:adverse effects / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D014652:Vascular Diseases / Q000139:chemically induced / Q000453:epidemiology
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011724:Pyridazines; D011743:Pyrimidines; C545373:ponatinib; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib; D000069439:Dasatinib
keywords: Arterial occlusive disease; BCR-ABL positive; chronic; leukemia; meta-analysis; myelogenous; protein kinase inhibitors; venous thrombosis