title: Factors Affecting Bleeding and Stent Thrombosis in Clinical Trials Comparing Bivalirudin With Heparin During Percutaneous Coronary Intervention.
abstract: BACKGROUND
  Patients treated with bivalirudin in randomized clinical trials of percutaneous coronary intervention generally have less bleeding but more acute stent thrombosis (ST) than do patients treated with heparin, but differences have varied among trials.
  
  
  RESULTS
  We modeled the risk of major hemorrhage and ischemic outcomes 30 days after percutaneous coronary intervention by treatment assignment and the use of adjunctive therapies in 18 randomized clinical trials enrolling 41,871 patients. Overall bivalirudin caused less major bleeding (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.53-0.76), more ST (OR, 1.58; 95% CI, 1.19-2.09), and no difference in mortality (OR, 0.93; 95% CI, 0.77-1.14) than heparin. A risk-benefit analysis identified 19 fewer bleeds and 5 more STs for every 1000 patients treated with bivalirudin in place of heparin. No significant bleeding advantage of bivalirudin over heparin could be identified in randomized clinical trials when transradial access (OR, 0.89; 95% CI, 0.57-1.41) and planned glycoprotein IIb/IIIa inhibitors were used with bivalirudin in the majority of patients (OR, 1.07; 95% CI, 0.87-1.31). The use of prasugrel or ticagrelor eliminated bleeding differences (OR, 0.80; 95% CI, 0.63-1.03) but did not reduce the risk of ST after bivalirudin (OR, 2.20; 95% CI, 1.48-3.27).
  
  
  CONCLUSIONS
  Substituting bivalirudin for heparin conferred a tradeoff between bleeding and ST. Transradial access, adjunctive glycoprotein IIb/IIIa inhibitors, and potent P2Y12 inhibitors attenuated the bleeding advantage of bivalirudin over heparin but had no apparent effect on early ST. New approaches to reduce bleeding and ischemic complications during percutaneous coronary intervention warrant further investigation.
authors.affiliation: From the Cardiac Catherization Laboratory, Munroe Regional Medical Center, Ocala, FL (J.A.B.); Office of Research and Methodology, National Center for Health Statistics, Hyattsville, MD (Y.H.); Division of Cardiology, Eastern Maine Medical Center, Bangor, ME (C.D.L.); and Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (G.D.D.). jabittl@mac.com.
authors.forename: John A
authors.initials: JA
authors.lastname: Bittl
authors.affiliation: From the Cardiac Catherization Laboratory, Munroe Regional Medical Center, Ocala, FL (J.A.B.); Office of Research and Methodology, National Center for Health Statistics, Hyattsville, MD (Y.H.); Division of Cardiology, Eastern Maine Medical Center, Bangor, ME (C.D.L.); and Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (G.D.D.).
authors.forename: Yulei
authors.initials: Y
authors.lastname: He
authors.affiliation: From the Cardiac Catherization Laboratory, Munroe Regional Medical Center, Ocala, FL (J.A.B.); Office of Research and Methodology, National Center for Health Statistics, Hyattsville, MD (Y.H.); Division of Cardiology, Eastern Maine Medical Center, Bangor, ME (C.D.L.); and Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (G.D.D.).
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Lang
authors.affiliation: From the Cardiac Catherization Laboratory, Munroe Regional Medical Center, Ocala, FL (J.A.B.); Office of Research and Methodology, National Center for Health Statistics, Hyattsville, MD (Y.H.); Division of Cardiology, Eastern Maine Medical Center, Bangor, ME (C.D.L.); and Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (G.D.D.).
authors.forename: George D
authors.initials: GD
authors.lastname: Dangas
mesh_terms: D002986:Clinical Trials as Topic; D006470:Hemorrhage / Q000209:etiology*; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D006629:Hirudins / Q000009:adverse effects; D006801:Humans; D009203:Myocardial Infarction / Q000209:etiology; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects* / Q000401:mortality; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D015607:Stents / Q000009:adverse effects*; D013927:Thrombosis / Q000209:etiology*
chemical_list: D006629:Hirudins; D010446:Peptide Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D058921:Purinergic P2Y Receptor Antagonists; D011994:Recombinant Proteins; D006493:Heparin; C074619:bivalirudin
keywords: bivalirudin; glycoproteins; heparin; percutaneous coronary intervention; platelet aggregation inhibitors