title: Clopidogrel in infants with systemic-to-pulmonary-artery shunts.
abstract: BACKGROUND
  Infants with cyanotic congenital heart disease palliated with placement of a systemic-to-pulmonary-artery shunt are at risk for shunt thrombosis and death. We investigated whether the addition of clopidogrel to conventional therapy reduces mortality from any cause and morbidity related to the shunt.
  
  
  METHODS
  In a multicenter, double-blind, event-driven trial, we randomly assigned infants 92 days of age or younger with cyanotic congenital heart disease and a systemic-to-pulmonary-artery shunt to receive clopidogrel at a dose of 0.2 mg per kilogram of body weight per day (467 infants) or placebo (439 infants), in addition to conventional therapy (including aspirin in 87.9% of infants). The primary efficacy end point was a composite of death or heart transplantation, shunt thrombosis, or performance of a cardiac procedure due to an event considered to be thrombotic in nature before 120 days of age.
  
  
  RESULTS
  The rate of the composite primary end point did not differ significantly between the clopidogrel group (19.1%) and the placebo group (20.5%) (absolute risk difference, 1.4 percentage points; relative risk reduction with clopidogrel, 11.1%; 95% confidence interval, -19.2 to 33.6; P=0.43), nor did the rates of the three components of the composite primary end point. There was no significant benefit of clopidogrel treatment in any subgroup, including subgroups defined by shunt type. Clopidogrel recipients and placebo recipients had similar rates of overall bleeding (18.8% and 20.2%, respectively) and severe bleeding (4.1% and 3.4%, respectively).
  
  
  CONCLUSIONS
  Clopidogrel therapy in infants with cyanotic congenital heart disease palliated with a systemic-to-pulmonary-artery shunt, most of whom received concomitant aspirin therapy, did not reduce either mortality from any cause or shunt-related morbidity. (Funded by Sanofi-Aventis and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00396877.).
authors.affiliation: Children's National Medical Center, Washington, DC 20010, USA. dwessel@childrensnational.org
authors.forename: David L
authors.initials: DL
authors.lastname: Wessel
authors.forename: Felix
authors.initials: F
authors.lastname: Berger
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Li
authors.forename: Ingo
authors.initials: I
authors.lastname: Dähnert
authors.forename: Amit
authors.initials: A
authors.lastname: Rakhit
authors.forename: Sylvie
authors.initials: S
authors.lastname: Fontecave
authors.forename: Jane W
authors.initials: JW
authors.lastname: Newburger
mesh_terms: D000714:Anastomosis, Surgical; D000077144:Clopidogrel; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006330:Heart Defects, Congenital / Q000401:mortality / Q000601:surgery*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000601:surgery; D013927:Thrombosis / Q000453:epidemiology / Q000517:prevention & control*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine