title: Prognostic modeling of individual patient risk and mortality impact of ischemic and hemorrhagic complications: assessment from the Acute Catheterization and Urgent Intervention Triage Strategy trial.
abstract: BACKGROUND
  Both ischemic and hemorrhagic complications increase mortality rate in acute coronary syndromes. Their frequency and relative importance vary according to individual patient risk profiles. We sought to develop prognostic models for the risk of myocardial infarction (MI) and major bleeding to assess their impact on risk of death and to examine the manner in which alternative antithrombotic regimens affect these risks in individual patients.
  
  
  RESULTS
  The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial randomized 13 819 patients with acute coronary syndrome to heparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone. By logistic regression, there were 5 independent predictors of MI within 30 days (n=705; 5.1%) and 8 independent predictors of major bleeding (n=645; 4.7%), only 2 of which were common to both event types. In a covariate-adjusted, time-updated Cox regression model, both MI and major bleeding significantly affected subsequent mortality rate (hazard ratios, 2.7 and 2.9, respectively; both P<0.001). Treatment with bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor was associated with a nonsignificant 8% increase in MI and a highly significant 50% decrease in major bleeding. Given the individual patient risk profiles and the fact that bivalirudin prevented approximately 6 major bleeds for each MI that might occur from its use, the estimated reduction in bleeding was greater than the estimated increase in MI by bivalirudin alone rather than heparin plus a glycoprotein IIb/IIIa inhibitor for nearly all patients.
  
  
  CONCLUSIONS
  Consideration of the individual patient risk profile for MI and major bleeding and the relative treatment effects of alternative pharmacotherapies permits personalized decision making to optimize therapy of patients with acute coronary syndrome.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00093158.
authors.affiliation: Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK. Stuart.Pocock@lshtm.ac.uk
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Pocock
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.forename: Tim C
authors.initials: TC
authors.lastname: Clayton
authors.forename: Eugenia
authors.initials: E
authors.lastname: Nikolsky
authors.forename: Helen
authors.initials: H
authors.lastname: Parise
authors.forename: Martin
authors.initials: M
authors.lastname: Fahy
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Lansky
authors.forename: Michel E
authors.initials: ME
authors.lastname: Bertrand
authors.forename: A Michael
authors.initials: AM
authors.lastname: Lincoff
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Moses
authors.forename: E Magnus
authors.initials: EM
authors.lastname: Ohman
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000401:mortality; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects*; D006470:Hemorrhage / Q000139:chemically induced* / Q000401:mortality*; D006493:Heparin / Q000009:adverse effects; D006629:Hirudins / Q000009:adverse effects; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000401:mortality; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000401:mortality*; D010446:Peptide Fragments / Q000009:adverse effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011237:Predictive Value of Tests; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D011994:Recombinant Proteins / Q000009:adverse effects; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D005343:Fibrinolytic Agents; D006629:Hirudins; D010446:Peptide Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D006493:Heparin; C074619:bivalirudin