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Context: Unfractionated heparin remains widely utilized in the treatment of acute coronary syndromes (ACS). However, limited data exist on optimal dosing and range of activated partial thromboplastin time (aPTT) in this setting. A large trial of thrombolysis for acute myocardial infarction has reported an association between longer aPTTs and adverse outcomes., Objectives: Estimate the optimal heparin-dosing regimen in achieving early therapeutic aPTTs (50 to 75 seconds) and determine the association of aPTT and death, reinfarction, and bleeding in population with ACS., Design: Subgroup analysis within a randomized, controlled trial of 5861 patients given unfractionated heparin who had aPTTs at 6, 12, or 24 hours, with outcome analyses by weight categories., Setting: In 373 hospitals in 13 countries from May 1994 to October 1995., Patients: A total of 12142 patients admitted for ACS, stratified by the presence (n = 4131) or absence (n = 8011) of ST-segment elevation, and randomized to 72 hours of unfractionated heparin., Results: In a simulated weight-adjusted model, based on retrospective grouping by weight, a simulated dose of 60-U/kg bolus and 12-U/kg/h infusion resulted in the highest proportion of therapeutic aPTTs. After adjustment for baseline variables, longer 12-hour aPTT was associated with the composite of 30-day death or reinfarction in patients not treated with thrombolytic therapy (odds ratio, 1.10; 95% CI, 1.00 to 1.22; P = 0.047). Longer aPTT at 6 hours was associated with increased moderate or severe bleeding for the entire cohort. There was also a significant, nonlinear correlation of the 12-hour aPTT with moderate or severe bleeding in thrombolysis-treated patients., Conclusions: For ACS patients who are treated with heparin, aPTT is highly associated with body weight. Longer aPTT within the first 12 hours is associated with adverse outcomes in ACS. Heparin dosing for ACS should be weight based.