title: An automated strategy for bedside aPTT determination and unfractionated heparin infusion adjustment in acute coronary syndromes: insights from PARAGON A.
abstract: BACKGROUND
  Intravenous unfractionated heparin remains a cornerstone of anticoagulation therapy for patients with acute coronary syndromes, but regulation to a target aPTT is challenging. We assessed unfractionated heparin infusion regulation by bedside, whole-blood aPTT testing and computerized, algorithmic infusion adjustment, and further evaluated the relationship of achieving the target aPTT with clinical outcomes.
  
  
  RESULTS
  We studied 1,275 patients randomized to unfractionated heparin in PARAGON-A, which tested lamifiban with or without unfractionated heparin versus unfractionated heparin. All patients had baseline and 6-hour blinded, bedside aPTTs, then aPTTs per algorithm. A central computer translated encrypted values to algorithmic dose-adjustment commands. We assessed the ability to achieve and maintain aPTTs of 50-70 seconds and associations of 6- and 12-hour aPTTs and time-to-target with 30-day outcomes.Overall, the median 6-hour aPTT was 50-70 seconds and remained so throughout infusion. Individually, only 33.6% of patients achieved 6-hour target-range aPTTs, and only 40% of all aPTTs were in-range. After achieving target, only 42% of subsequent measures were in-range. Thirty-day death or myocardial infarction (death/MI) increased non-significantly as time-to-target increased (p = 0.08). Thirty-day mortality was similar if target aPTT was reached, regardless of timing. Death/MI trended lower if target aPTT was reached by 8 hours (p = 0.10). The best clinical outcomes were associated with in-range aPTTs.
  
  
  CONCLUSIONS
  This study represents the most systematic monitoring and regulation of unfractionated heparin anticoagulation to date. Although average anticoagulation achieved target range, wide inter- and intra-patient variability may have important implications for clinical outcomes.
authors.affiliation: Duke Clinical Research Institute, Durham, NC 27715-7969, USA. newby001@mc.duke.edu
authors.forename: L Kristin
authors.initials: LK
authors.lastname: Newby
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: Manjushri V
authors.initials: MV
authors.lastname: Bhapkar
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
authors.forename: Judith S
authors.initials: JS
authors.lastname: Hochman
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.forename: R John
authors.initials: RJ
authors.lastname: Simes
authors.forename: Catherine G
authors.initials: CG
authors.lastname: Davis
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: David J
authors.initials: DJ
authors.lastname: Moliterno
mesh_terms: D000085:Acetates / Q000627:therapeutic use; D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006493:Heparin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods / Q000706:statistics & numerical data; D016017:Odds Ratio; D010314:Partial Thromboplastin Time; D019095:Point-of-Care Systems / Q000706:statistics & numerical data*; D013577:Syndrome; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000085:Acetates; C078918:ITF 300; D014443:Tyrosine; D006493:Heparin; C084062:lamifiban