title: Risk of Stent Thrombosis and Major Bleeding with Bivalirudin Compared with Active Control: A Systematic Review and Meta-analysis of Randomized Trials.
abstract: BACKGROUND
  Bivalirudin is commonly used for patients undergoing percutaneous coronary intervention (PCI), but there have been recent concerns that it may be associated with an increased risk of stent thrombosis and provide no benefit regarding major bleeding compared with active control.
  
  
  RESULTS
  We searched PubMed, clinicaltrials.gov, and conference proceedings for randomized controlled trials of bivalirudin versus active control in patients undergoing PCI. The main outcomes of interest were definite stent thrombosis, myocardial infarction, major bleeding, and mortality. We used random-effects modeling to pool the data. We included 25 trials involving 41,243 patients. Overall, use of bivalirudin compared with active control was associated with an increased risk of definite stent thrombosis (11 trials; 16,864 patients; RR, 1.73; 95% CI, 1.24-2.40; P<0.001; I(2)=0%), similar risk of acute myocardial infarction (22 trials; 40,578 patients; RR, 1.00; 95% CI, 0.87-1.16; P=0.96; I(2)=43%), decreased risk of major bleeding (25 trials; 41,243 patients; RR, 0.59; 95% CI, 0.49-0.72; P<0.001; I(2)=31%) and of cardiac death (6 trials; 6,956 patients; RR, 0.72; 95% CI, 0.53-0.99; P=0.05; I(2)=0%), but no change in all-cause mortality (24 trials; 41,058 patients; RR, 0.96; 95% CI, 0.81-1.15; P=0.69; I(2)=0%). Results were consistent across a wide set of subgroup and sensitivity analyses.
  
  
  CONCLUSIONS
  Compared with active control, bivalirudin is associated with increased risk of stent thrombosis but lower risk of major bleeding, with no discernible impact on all-cause mortality.
authors.affiliation: School of Public Health, Yale University, New Haven, CT, United States.
authors.forename: Sina
authors.initials: S
authors.lastname: Kianoush
authors.affiliation: Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, CT, United States; Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, Unites States. Electronic address: Behnood.bikdeli@yale.edu.
authors.forename: Behnood
authors.initials: B
authors.lastname: Bikdeli
authors.affiliation: Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, CT, United States; Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, Unites States; Robert Wood Johnson Clinical Scholars Program, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, United States.
authors.forename: Mayur M
authors.initials: MM
authors.lastname: Desai
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
mesh_terms: D000991:Antithrombins / Q000009:adverse effects*; D006470:Hemorrhage / Q000139:chemically induced*; D006629:Hirudins / Q000009:adverse effects*; D006801:Humans; D010446:Peptide Fragments / Q000009:adverse effects*; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects*; D011994:Recombinant Proteins / Q000009:adverse effects; D012306:Risk; D015607:Stents / Q000009:adverse effects*; D013927:Thrombosis / Q000209:etiology*
chemical_list: D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C074619:bivalirudin
keywords: Acute Myocardial Infarction; Bivalirudin; Bleeding; Mortality; Stent