title: Predictors of initial nontherapeutic anticoagulation with unfractionated heparin in ST-segment elevation myocardial infarction.
abstract: BACKGROUND
  Although weight-based nomograms have improved the efficacy and safety of dosing unfractionated heparin in ST-segment elevation myocardial infarction, achieving therapeutic anticoagulation in practice remains challenging.
  
  
  RESULTS
  In the Enoxaparin and Thrombolysis in Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis in Myocardial Infarction (ExTRACT-TIMI) 25 study, 20 506 patients with ST-segment elevation myocardial infarction were randomized to enoxaparin or unfractionated heparin, the latter dosed according to the American College of Cardiology/American Heart Association weight-based nomogram with centrally monitored activated partial thromboplastin times (aPTTs). A total of 6055 patients received study unfractionated heparin and a fibrin-specific lytic and had an initial aPTT drawn within 4 to 8 hours of starting therapy. Despite close adherence to recommended dosing, only 33.8% of initial aPTTs were therapeutic (1.50 to 2.00 times control); 13.2% were markedly low (<1.25 times); and 16.3% were markedly high (> or =2.75 times). Markedly high aPTTs were more likely in patients who were older (adjusted risk ratio [RR(adj)], 1.14 per decade; P=0.001), were female (RR(adj), 1.46; P<0.001), were of lower weight (RR(adj), 1.19 per 10-kg decrease; P<0.001) or had renal dysfunction (RR(adj), 1.08 per 0.2-mg/dL increase in serum creatinine; P=0.006). Markedly high aPTTs were associated with increased risk of TIMI major or minor bleeding by 48 hours (odds ratio, 2.11; P=0.004); markedly low aPTTs tended to be associated with increased risk of fatal or nonfatal reinfarction by 48 hours (odds ratio, 2.19; P=0.057).
  
  
  CONCLUSIONS
  Despite the use of a standard weight-based unfractionated heparin nomogram in ST-segment elevation myocardial infarction, nontherapeutic anticoagulation is frequent and more likely among certain vulnerable patient groups, with excess anticoagulation associated with increased bleeding and inadequate anticoagulation associated with reinfarction. These findings should be considered when dosing unfractionated heparin in support of fibrinolytic therapy.
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Cheng
authors.forename: David A
authors.initials: DA
authors.lastname: Morrow
authors.forename: Sarah
authors.initials: S
authors.lastname: Sloan
authors.forename: Elliott M
authors.initials: EM
authors.lastname: Antman
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001777:Blood Coagulation / Q000187:drug effects; D003324:Coronary Artery Disease / Q000188:drug therapy; D003328:Coronary Thrombosis / Q000517:prevention & control*; D004562:Electrocardiography; D017984:Enoxaparin / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy*; D010314:Partial Thromboplastin Time; D011237:Predictive Value of Tests; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D006493:Heparin