title: Comprehensive meta-analysis of safety and efficacy of bivalirudin versus heparin with or without routine glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndrome.
abstract: OBJECTIVE
  The aim of this meta-analysis was to compare the 30-day safety and efficacy of bivalirudin with those of heparin with or without routine administration of a glycoprotein IIb/IIIa inhibitor (GPI) in patients with acute coronary syndrome (ACS).
  
  
  BACKGROUND
  Bivalirudin has been a mainstay of anticoagulation in patients with ACS compared with heparin. The extent to which trial results have been affected by the coadministration of heparin with a GPI, however, remains unclear.
  
  
  METHODS
  A total of 13 randomized, controlled trials involving 24,605 patients were included.
  
  
  RESULTS
  There was no significant difference in 30-day mortality or myocardial infarction rate with bivalirudin compared with heparin with or without routine GPI administration. A reduction of 30-day major bleeding was observed with bivalirudin compared with heparin that was significant when GPI was routinely administered (odds ratio [OR]: 0.52, 95% confidence interval [CI]: 0.45 to 0.60), p < 0.001) but not with provisionally administered GPI (OR: 0.66, 95% CI: 0.33 to 1.32; p = 0.24). The occurrence of stent thrombosis (ST) at 30 days was significantly increased with bivalirudin compared with heparin plus routinely administered GPI (OR: 1.67, 95% CI: 1.13 to 2.45, p = 0.02), but not compared with heparin plus provisionally administered GPI (OR: 2.08, 95% CI: 0.35 to 12.32, p = 0.42). The rate of acute ST (≤ 24 h), however, was almost 4.5-fold higher with bivalirudin compared with heparin with or without GPI, whereas the rate of subacute ST (24 h to 30 days) did not differ significantly.
  
  
  CONCLUSIONS
  Overall, bivalirudin in ACS patients is associated with a significant reduction of major bleeding compared with heparin plus routinely administered GPI, but with a marked increase in ST rates compared with heparin with or without GPI.
authors.affiliation: Invasive Cardiology, National Research Council Institute of Clinical Physiology, Pisa, Italy; Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany; Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Research Network, Poland and Germany. Electronic address: eliano.navarese@alice.it.
authors.forename: Eliano Pio
authors.initials: EP
authors.lastname: Navarese
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany; Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Research Network, Poland and Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Schulze
authors.affiliation: Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Research Network, Poland and Germany; Department of Cardiovascular Science, Catholic University, Rome, Italy.
authors.forename: Felicita
authors.initials: F
authors.lastname: Andreotti
authors.affiliation: Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Research Network, Poland and Germany; Department of Cardiology, 10th Military Research Hospital and Polyclinic, Bydgoszcz, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Kowalewski
authors.affiliation: Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Research Network, Poland and Germany; Department of Cardiology and Internal Medicine, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Michalina
authors.initials: M
authors.lastname: Kołodziejczak
authors.affiliation: Piedmont Heart Institute, Atlanta, Georgia.
authors.forename: David E
authors.initials: DE
authors.lastname: Kandzari
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany; Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Research Network, Poland and Germany.
authors.forename: Tienush
authors.initials: T
authors.lastname: Rassaf
authors.affiliation: Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Research Network, Poland and Germany; Department of Cardiovascular Science, Catholic University, Rome, Italy.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Gorny
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany; Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Research Network, Poland and Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Brockmeyer
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany; Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Research Network, Poland and Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Meyer
authors.affiliation: Invasive Cardiology, National Research Council Institute of Clinical Physiology, Pisa, Italy; Cardiothoracic Department, Heart Hospital, Fondazione Toscana Gabriele Monasterio, Massa, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Berti
authors.affiliation: Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Research Network, Poland and Germany; Department of Cardiology and Internal Medicine, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Kubica
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany; Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Research Network, Poland and Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
authors.affiliation: Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: Valgimigli
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D016009:Chi-Square Distribution; D003328:Coronary Thrombosis / Q000209:etiology / Q000517:prevention & control; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D006629:Hirudins / Q000009:adverse effects; D006801:Humans; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D016017:Odds Ratio; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D006629:Hirudins; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D006493:Heparin; C074619:bivalirudin
keywords: GP IIb/IIIa inhibitor; acute coronary syndrome; bivalirudin; heparin; meta-analysis