title: Reappraisal of thienopyridine pretreatment in patients with non-ST elevation acute coronary syndrome: a systematic review and meta-analysis.
abstract: OBJECTIVE
  To investigate the effect of pretreatment with P2Y12 receptor inhibitors compared with no pretreatment on efficacy and safety of treatment of non-ST elevation acute coronary syndrome (ACS).
  
  
  METHODS
  Two reviewers independently searched Medline, Embase, Cochrane Controlled Trials, and BioMed Central databases for randomized placebo controlled trials and observational studies from August 2001 to March 2014.
  
  
  METHODS
  Studies must have reported both all-cause mortality (primary efficacy endpoint) and major bleeding (safety endpoint) outcomes.
  
  
  METHODS
  Data on sample size, characteristics, drug dose and delay of administration, and outcomes were independently extracted and analyzed.
  
  
  RESULTS
  A random-effect model was applied. The analysis was performed (i) in all patients independently of the management strategy and (ii) only in patients undergoing percutaneous coronary intervention.
  
  
  RESULTS
  Of the 393 titles identified, seven (four randomized controlled trials, one observational analysis from a randomized controlled trial, and three observational studies) met the inclusion criteria. No study was identified for ticagrelor or cangrelor, and analyses were thus limited to thienopyridines. A total of 32,383 non-ST elevation ACS patients were included, 18,711 coming from randomized controlled trials. Of these, 55% underwent percutaneous coronary intervention (PCI). Pretreatment was not associated with a significant lower risk of mortality in all patients (odds ratio 0.90 (95% confidence interval 0.75 to 1.07), P=0.24), in particular when considering only the randomized controlled trials (odds ratio 0.90 (0.71 to 1.14), P=0.39). Similar results were observed in the cohort of patients undergoing PCI. A significant 30-45% excess of major bleeding was consistently observed in all patients (odds ratio 1.32 (1.16 to 1.49), P<0.0001) and in those undergoing PCI, as well as in the subset analyses of randomized controlled trials of these two cohorts of patients. There was a reduction in major adverse cardiovascular events in the analysis of all patients (odds ratio 0.84 (0.72 to 0.98), P=0.02), driven by the old clopidogrel studies (CURE and CREDO), but the difference was not significant for the cohort of patients undergoing PCI. Stent thrombosis, stroke, and urgent revascularization did not differ between groups (pretreatment v no pretreatment). The results were consistent for both thienopyridines and confirmed in sensitivity analyses.
  
  
  CONCLUSIONS
  Analysis was not performed on individual patient's data.
  
  
  CONCLUSIONS
  In patients presenting with non-ST elevation ACS, pretreatment with thienopyridines is associated with no significant reduction of mortality but with a significant excess of major bleeding no matter the strategy adopted, invasive or not. Our results do not support a strategy of routine pretreatment in patients with non-ST elevation ACS.
authors.affiliation: Service de Cardiologie-La Fontonne Hospital, Antibes, France ACTION Study Group, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Bellemain-Appaix
authors.affiliation: Institut de Cardiologie, INSERM UMRS1166, Pitié-Salpêtrière Hospital (AP-HP), Université Paris 6, France ACTION Study Group, Paris, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Kerneis
authors.affiliation: Institut de Cardiologie, INSERM UMRS1166, Pitié-Salpêtrière Hospital (AP-HP), Université Paris 6, France ACTION Study Group, Paris, France.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: O'Connor
authors.affiliation: Institut de Cardiologie, INSERM UMRS1166, Pitié-Salpêtrière Hospital (AP-HP), Université Paris 6, France ACTION Study Group, Paris, France.
authors.forename: Johanne
authors.initials: J
authors.lastname: Silvain
authors.affiliation: UMR CNRS 5558, Université Lyon 1 Laennec, Lyon, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Cucherat
authors.affiliation: Institut de Cardiologie, INSERM UMRS1166, Pitié-Salpêtrière Hospital (AP-HP), Université Paris 6, France ACTION Study Group, Paris, France.
authors.forename: Farzin
authors.initials: F
authors.lastname: Beygui
authors.affiliation: Institut de Cardiologie, INSERM UMRS1166, Pitié-Salpêtrière Hospital (AP-HP), Université Paris 6, France ACTION Study Group, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Barthélémy
authors.affiliation: Institut de Cardiologie, INSERM UMRS1166, Pitié-Salpêtrière Hospital (AP-HP), Université Paris 6, France ACTION Study Group, Paris, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Collet
authors.affiliation: Service de Cardiologie-La Fontonne Hospital, Antibes, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Jacq
authors.affiliation: Service de Cardiologie-La Fontonne Hospital, Antibes, France.
authors.forename: François
authors.initials: F
authors.lastname: Bernasconi
authors.affiliation: Institut de Cardiologie, INSERM UMRS1166, Pitié-Salpêtrière Hospital (AP-HP), Université Paris 6, France ACTION Study Group, Paris, France gilles.montalescot@psl.aphp.fr.
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D006801:Humans; D015233:Models, Statistical; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C446540:thienopyridine