title: Dabigatran etexilate and risk of myocardial infarction, other cardiovascular events, major bleeding, and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  Signals of an increased risk of myocardial infarction (MI) have been identified with dabigatran etexilate in randomized controlled trials (RCTs).
  We conducted searches of the published literature and a clinical trials registry maintained by the drug manufacturer. Criteria for inclusion in our meta-analysis included all RCTs and the availability of outcome data for MI, other cardiovascular events, major bleeding, and all-cause mortality. Among the 501 unique references identified, 14 RCTs fulfilled the inclusion criteria. Stratification analyses by comparators and doses of dabigatran etexilate were conducted. Peto odds ratio (ORPETO) values using the fixed-effect model (FEM) for MI, other cardiovascular events, major bleeding, and all-cause mortality were 1.34 (95% CI 1.08 to 1.65, P=0.007), 0.93 (95%CI 0.83 to 1.06, P=0.270), 0.88 (95% CI 0.79 to 0.99, P=0.029), and 0.89 (95% CI 0.80 to 1.00, P=0.041). When compared with warfarin, ORPETO values using FEM were 1.41 (95% CI 1.11 to 1.80, P=0.005), 0.94 (95%CI 0.83 to 1.06, P=0.293), 0.85 (95% CI 0.76 to 0.96, P=0.007), and 0.90 (95% CI 0.81 to 1.01, P=0.061), respectively. In RCTs using the 150-mg BID dosage, the ORPETO values using FEM were 1.45 (95% CI 1.11 to 1.91, P=0.007), 0.95 (95% CI 0.82 to 1.09, P=0.423), 0.92 (95% CI 0.81 to 1.05, P=0.228), and 0.88 (95% CI 0.78 to 1.00, P=0.045), respectively. The results of the 110-mg BID dosage were mainly driven by the RE-LY trial.
  
  
  CONCLUSIONS
  This meta-analysis provides evidence that dabigatran etexilate is associated with a significantly increased risk of MI. This increased risk should be considered taking into account the overall benefit in terms of major bleeding and all-cause mortality.
authors.affiliation: Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Namur, Belgium (J.D., F.M., V.M., J.M.D.).
authors.forename: Jonathan
authors.initials: J
authors.lastname: Douxfils
authors.affiliation: Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium (F.B., R., J.Y.R., O.B.).
authors.forename: Fanny
authors.initials: F
authors.lastname: Buckinx
authors.affiliation: Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Namur, Belgium (J.D., F.M., V.M., J.M.D.) Hematology Laboratory, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), CHU Dinant-Godinne UCL Namur, Yvoir, Belgium (F.M.).
authors.forename: François
authors.initials: F
authors.lastname: Mullier
authors.affiliation: Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Namur, Belgium (J.D., F.M., V.M., J.M.D.).
authors.forename: Valentine
authors.initials: V
authors.lastname: Minet
authors.affiliation: Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium (F.B., R., J.Y.R., O.B.).
authors.forename: Véronique
authors.initials: V
authors.lastname: Rabenda
authors.affiliation: Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium (F.B., R., J.Y.R., O.B.).
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Reginster
authors.affiliation: Department of General Internal Medicine, Cliniques Universitaires Saint Luc, UCL, Bruxelles, Belgium (P.H.).
authors.forename: Philippe
authors.initials: P
authors.lastname: Hainaut
authors.affiliation: Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium (F.B., R., J.Y.R., O.B.).
authors.forename: Olivier
authors.initials: O
authors.lastname: Bruyère
authors.affiliation: Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Namur, Belgium (J.D., F.M., V.M., J.M.D.).
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dogné
mesh_terms: D001562:Benzimidazoles / Q000009:adverse effects* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D000069604:Dabigatran; D065427:Factor Xa Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D009026:Mortality; D009203:Myocardial Infarction / Q000139:chemically induced*; D011725:Pyridines / Q000009:adverse effects* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000517:prevention & control
chemical_list: D001562:Benzimidazoles; D065427:Factor Xa Inhibitors; D011725:Pyridines; D000069604:Dabigatran
keywords: all‐cause mortality; dabigatran etexilate; major bleeding; myocardial infarction