title: A multicenter, randomized trial comparing heparin/warfarin and acetylsalicylic acid as primary thromboprophylaxis for 2 years after the Fontan procedure in children.
abstract: OBJECTIVE
  The purpose of this study was to compare the safety and efficacy of acetylsalicylic acid (ASA) and warfarin for thromboprophylaxis after the Fontan procedure.
  
  
  BACKGROUND
  Fontan surgery is the definitive palliation for children with single-ventricle physiology. Thrombosis is an important complication; the optimal thromboprophylaxis strategy has not been determined.
  
  
  METHODS
  We performed a multicenter international randomized trial of primary prophylactic anticoagulation after Fontan surgery. Patients were randomized to receive for 2 years either ASA (5 mg/kg/day, no heparin phase) or warfarin (started within 24 h of heparin lead-in; target international normalized ratio: 2.0 to 3.0). Primary endpoint (intention to treat) was thrombosis, intracardiac or embolic (all events adjudicated). At 3 months and 2 years after the Fontan procedure, transthoracic and transesophageal echocardiograms were obtained as routine surveillance. Major bleeding and death were primary adverse outcomes.
  
  
  RESULTS
  A total of 111 eligible patients were randomized (57 to ASA, 54 to heparin/warfarin). Baseline characteristics for each group were similar. There were 2 deaths unrelated to thrombosis or bleeding. There were 13 thromboses in the heparin/warfarin group (3 clinical, 10 routine echo) and 12 thromboses in the ASA group (4 clinical, 8 routine echo). Overall freedom from thrombosis 2 years after Fontan surgery was 19%, despite thrombosis prophylaxis. Cumulative risk of thrombosis was persistent but varying and similar for both groups (p = 0.45). Major bleeding occurred in 1 patient in each group.
  
  
  CONCLUSIONS
  There was no significant difference between ASA and heparin/warfarin as primary thromboprophylaxis in the first 2 years after Fontan surgery. The thrombosis rate was suboptimal for both regimens, suggesting alternative approaches should be considered. (International Multi Centre Randomized Clinical Trial Of Anticoagulation In Children Following Fontan Procedures; NCT00182104).
authors.affiliation: Department of Paediatrics, University of Melbourne, Royal Children's Hospital and Critical Care and Neurosciences Theme, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Monagle
authors.forename: Andrew
authors.initials: A
authors.lastname: Cochrane
authors.forename: Robin
authors.initials: R
authors.lastname: Roberts
authors.forename: Cedric
authors.initials: C
authors.lastname: Manlhiot
authors.forename: Robert
authors.initials: R
authors.lastname: Weintraub
authors.forename: Barbara
authors.initials: B
authors.lastname: Szechtman
authors.forename: Marina
authors.initials: M
authors.lastname: Hughes
authors.forename: Maureen
authors.initials: M
authors.lastname: Andrew
authors.forename: Brian W
authors.initials: BW
authors.lastname: McCrindle
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D004452:Echocardiography / Q000379:methods; D005260:Female; D018729:Fontan Procedure / Q000379:methods*; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D007391:International Cooperation; D008297:Male; D013923:Thromboembolism / Q000188:drug therapy; D013927:Thrombosis / Q000188:drug therapy; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D006493:Heparin; D001241:Aspirin