title: Association of clopidogrel pretreatment with mortality, cardiovascular events, and major bleeding among patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis.
abstract: BACKGROUND
  Clopidogrel pretreatment is recommended for patients with acute coronary syndromes (ACS) and stable coronary artery disease who are scheduled for percutaneous coronary intervention (PCI), but whether using clopidogrel as a pretreatment for PCI is associated with positive clinical outcomes has not been established.
  
  
  OBJECTIVE
  To evaluate the association of clopidogrel pretreatment vs no treatment with mortality and major bleeding after PCI.
  
  
  METHODS
  MEDLINE, EMBASE, Cochrane Controlled Trials Register databases, and reference lists of qualifying articles. STUDY SELECTION Studies reporting clinical data on mortality and major bleeding were included. Of the 392 titles identified, 15 articles published between August 2001 and September 2012 met the inclusion criteria: 6 randomized controlled trials (RCTs), 2 observational analyses of RCTs, and 7 observational studies.
  
  
  METHODS
  Quality of studies was assessed with the Ottawa Scale and the Jadad Score as appropriate. Results were independently extracted by 2 reviewers. A random-effect model was applied. Pretreatment was defined as the administration of clopidogrel before PCI or catheterization. The main analysis was performed on RCTs and confirmed by observational analyses and observational studies. Prespecified subgroups--clinical presentation and clopidogrel loading dose--were analyzed. The primary efficacy and safety end points were all-cause mortality and major bleeding. Secondary end points included major cardiac events.
  
  
  RESULTS
  Of the 37 814 patients included in the meta-analysis, 8608 patients had participated in RCTs; 10,945, in observational analyses of RCTs; and 18,261, in observational studies. Analysis of RCTs showed that clopidogrel pretreatment was not associated with a reduction of death (absolute risk, 1.54% vs 1.97%; OR, 0.80; 95% CI, 0.57-1.11; P = .17) but was associated with a lower risk of major cardiac events (9.83% vs 12.35%; OR, 0 .77; 95% CI, 0.66-0.89; P < .001). There was no significant association between pretreatment and major bleeding overall (3 .57% vs 3.08%; OR, 1.18; 95% CI, 0.93-1.50; P = .18). Analyses from observational analyses of RCTs and observational studies were consistent for all results.
  
  
  CONCLUSIONS
  Among patients scheduled for PCI, clopidogrel pretreatment was not associated with a lower risk of mortality but was associated with a lower risk of major coronary events.
authors.affiliation: Service de Cardiologie-La FontonneHospital, Antibes, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Bellemain-Appaix
authors.forename: Stephen A
authors.initials: SA
authors.lastname: O'Connor
authors.forename: Johanne
authors.initials: J
authors.lastname: Silvain
authors.forename: Michel
authors.initials: M
authors.lastname: Cucherat
authors.forename: Farzin
authors.initials: F
authors.lastname: Beygui
authors.forename: Olivier
authors.initials: O
authors.lastname: Barthélémy
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Collet
authors.forename: Laurent
authors.initials: L
authors.lastname: Jacq
authors.forename: François
authors.initials: F
authors.lastname: Bernasconi
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
mesh_terms: D054058:Acute Coronary Syndrome / Q000628:therapy; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000628:therapy; D023381:Endpoint Determination; D006470:Hemorrhage / Q000517:prevention & control*; D006801:Humans; D009203:Myocardial Infarction / Q000517:prevention & control; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000401:mortality*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011300:Preoperative Care; D016032:Randomized Controlled Trials as Topic; D012042:Registries; D020521:Stroke / Q000517:prevention & control; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine