title: Relationship between heparin anticoagulation and clinical outcomes in coronary stent intervention: observations from the ESPRIT trial.
abstract: OBJECTIVE
  We evaluated the relationship between the degree of heparin anticoagulation and clinical efficacy and bleeding in patients undergoing contemporary percutaneous coronary intervention (PCI) with stent implantation.
  
  
  BACKGROUND
  Despite universal acceptance of heparin anticoagulation as a standard of care in PCI, considerable controversy still exists regarding the appropriate dosing of heparin.
  
  
  METHODS
  The study population (n = 2,064) comprised all patients enrolled in the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial. The index activated clotting time (ACT) was defined as the ACT measured after the last heparin dose and before first device activation and was correlated with outcome and bleeding events.
  
  
  RESULTS
  No association was observed between decreasing ACT levels and the rate of ischemic events in the treatment or placebo arms. The incidence of the primary composite end point (death, myocardial infarction, urgent target vessel revascularization, and thrombotic bailout glycoprotein IIb/IIIa inhibitor therapy at 48 h) was actually lowest in the lowest ACT tertile for both the placebo (10.0%) and treatment groups (6.1%). When analyzed by tertile, major bleeding rates did not increase in the lowest ACT tertile in patients given placebo (0.6%) versus those receiving eptifibatide (0.7%). Major bleeding rates increased as the ACT increased in the eptifibatide-treated patients.
  
  
  CONCLUSIONS
  Ischemic end points in patients undergoing contemporary PCI with stent placement do not increase by decreasing ACT levels, at least to a level of 200 s. Bleeding events do increase with increasing ACT levels and are enhanced with eptifibatide treatment. An ACT of 200 to 250 s is reasonable in terms of efficacy and safety with the use of contemporary technology and pharmacotherapy.
authors.affiliation: Duke University Medical Center and Clinical Research Institute, Durham, NC 27705, USA.
authors.forename: Thaddeus R
authors.initials: TR
authors.lastname: Tolleson
authors.forename: J Conor
authors.initials: JC
authors.lastname: O'Shea
authors.forename: John A
authors.initials: JA
authors.lastname: Bittl
authors.forename: William B
authors.initials: WB
authors.lastname: Hillegass
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Williams
authors.forename: Glenn
authors.initials: G
authors.lastname: Levine
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: James E
authors.initials: JE
authors.lastname: Tcheng
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects*; D003324:Coronary Artery Disease / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000209:etiology*; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D017063:Outcome Assessment, Health Care; D015607:Stents / Q000009:adverse effects*; D014914:Whole Blood Coagulation Time
chemical_list: D000925:Anticoagulants; D006493:Heparin