title: Prolonged High-Dose Bivalirudin Infusion Reduces Major Bleeding Without Increasing Stent Thrombosis in Patients Undergoing Primary Percutaneous Coronary Intervention: Novel Insights From an Updated Meta-Analysis.
abstract: The optimal antithrombotic therapy in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI) remains a matter of debate. This updated meta-analysis investigated the impact of (1) bivalirudin (with and without prolonged infusion) and (2) prolonged PCI-dose (1.75 mg/hg per hour) bivalirudin infusion compared with conventional antithrombotic therapy on clinical outcomes in patients undergoing primary PCI.
  
  
  
  Eligible randomized trials were searched through MEDLINE, EMBASE, Cochrane database, and proceedings of major congresses. Prespecified outcomes were major bleeding (thrombolysis in myocardial infarction major and Bleeding Academic Research Consortium 3-5), acute stent thrombosis, as well as all-cause and cardiac mortality at 30 days. Six randomized trials (n=17 294) were included. Bivalirudin compared with heparin (+/- glycoprotein-IIb/IIIa inhibitor) was associated with reduction in major bleeding (odds ratio [OR]: 0.65, 95% CI: 0.48-0.88, P=0.006, derived from all 6 trials), increase in acute stent thrombosis (OR: 2.75, 95% CI: 1.46-5.18, P=0.002, 5 trials), and lower rate of all-cause mortality (OR: 0.81, 95% CI: 0.67-0.98, P=0.03, 6 trials) as well as cardiac mortality (OR: 0.69, 95% CI: 0.55-0.87, P=0.001, 5 trials). The incidence of acute stent thrombosis did not differ between the prolonged PCI-dose bivalirudin and comparator group (OR: 0.81, 95% CI: 0.27-2.46, P=0.71, 3 trials), whereas the risk of bleeding was reduced despite treatment with high-dose bivalirudin infusion (OR: 0.28, 95% CI: 0.13-0.60, P=0.001, 3 trials).
  
  
  
  Bivalirudin (with and without prolonged infusion) compared with conventional antithrombotic therapy in ST-segment-elevation myocardial infarction patients undergoing primary PCI reduces major bleeding and death, but increases the rate of acute stent thrombosis. However, prolonging the bivalirudin infusion at PCI-dose (1.75 mg/kg per hour) for 3 hours eliminates the excess risk of acute stent thrombosis, while maintaining the bleeding benefits.
authors.affiliation: Oxford Heart Centre, The John Radcliffe Hospital, Oxford University Hospitals, Oxford, UK.
authors.forename: Gregor
authors.initials: G
authors.lastname: Fahrni
authors.affiliation: Oxford Heart Centre, The John Radcliffe Hospital, Oxford University Hospitals, Oxford, UK.
authors.forename: Mathias
authors.initials: M
authors.lastname: Wolfrum
authors.affiliation: Oxford Heart Centre, The John Radcliffe Hospital, Oxford University Hospitals, Oxford, UK.
authors.forename: Giovanni Luigi
authors.initials: GL
authors.lastname: De Maria
authors.affiliation: Oxford Heart Centre, The John Radcliffe Hospital, Oxford University Hospitals, Oxford, UK.
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Banning
authors.affiliation: Bristol Heart Institute, School of Clinical Sciences, University of Bristol, UK.
authors.forename: Umberto
authors.initials: U
authors.lastname: Benedetto
authors.affiliation: Oxford Heart Centre, The John Radcliffe Hospital, Oxford University Hospitals, Oxford, UK rajesh.kharbanda@ouh.nhs.uk.
authors.forename: Rajesh K
authors.initials: RK
authors.lastname: Kharbanda
mesh_terms: D000991:Antithrombins / Q000008:administration & dosage / Q000009:adverse effects*; D006470:Hemorrhage / Q000139:chemically induced*; D006629:Hirudins / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007262:Infusions, Intravenous; D016017:Odds Ratio; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects*; D062645:Percutaneous Coronary Intervention / Q000379:methods*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D000072657:ST Elevation Myocardial Infarction / Q000628:therapy*; D015607:Stents; D013927:Thrombosis / Q000517:prevention & control*
chemical_list: D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C074619:bivalirudin
keywords: bivalirudin; meta‐analysis; myocardial infarction; percutaneous coronary intervention