title: Defining the optimal activated clotting time during percutaneous coronary intervention: aggregate results from 6 randomized, controlled trials.
abstract: BACKGROUND
  Unfractionated heparin has been the primary anticoagulant therapy for percutaneous coronary intervention for >20 years. Despite the availability of rapid "point of care" testing, little clinical data defining the optimal level of anticoagulation are available. Furthermore, recent reports have advocated the use of low-dose heparin regimens in the absence of large-scale, well-conducted studies to support this practice.
  
  
  RESULTS
  We pooled the data from 6 randomized, controlled trials of novel adjunctive antithrombotic regimens for percutaneous coronary interventions in which unfractionated heparin constituted the control arm. Patients were divided into 25-s intervals of activated clotting times (ACTs), from <275 s to >476 s. In a total of 5216 patients, the incidence of death, myocardial infarction, or any revascularization and major or minor bleeding at 7 days were calculated for each group and compared. An ACT in the range of 350 to 375 s provided the lowest composite ischemic event rate of 6.6%, or a 34% relative risk reduction in 7-day ischemic events compared with rates observed between 171 and 295 s by quartile analysis (P=0.001).
  
  
  CONCLUSIONS
  Contrary to recent reports, the optimal suppression of ischemic events with unfractionated heparin therapy in patients undergoing percutaneous coronary intervention demands treatment to ACT levels that are substantially higher than currently appreciated. These data define a goal for heparin dosing within coronary interventions and establish a benchmark of optimal unfractionated heparin therapy against which future trials of novel antithrombotic regimens in percutaneous interventions can be compared.
authors.affiliation: Department of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: Chew
authors.forename: D L
authors.initials: DL
authors.lastname: Bhatt
authors.forename: A M
authors.initials: AM
authors.lastname: Lincoff
authors.forename: D J
authors.initials: DJ
authors.lastname: Moliterno
authors.forename: S J
authors.initials: SJ
authors.lastname: Brener
authors.forename: K E
authors.initials: KE
authors.lastname: Wolski
authors.forename: E J
authors.initials: EJ
authors.lastname: Topol
mesh_terms: D000077284:Abciximab; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D003327:Coronary Disease / Q000150:complications / Q000601:surgery; D003710:Demography; D048909:Diabetes Complications; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006470:Hemorrhage / Q000209:etiology; D006493:Heparin / Q000009:adverse effects / Q000592:standards* / Q000627:therapeutic use; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D015994:Incidence; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D018570:Risk Assessment; D012307:Risk Factors; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome; D014914:Whole Blood Coagulation Time
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D006493:Heparin; D000077284:Abciximab