title: Impact of clopidogrel loading dose on clinical outcome in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis.
abstract: BACKGROUND
  Enhanced platelet inhibition by clopidogrel decreases the risk of ischemic events but carries a risk for a concomitant increase in bleeding.
  
  
  OBJECTIVE
  To compare the efficacy and safety of two clopidogrel loading regimens (300mg vs. 600mg) in patients undergoing percutaneous coronary intervention (PCI) at one month after start of therapy.
  
  
  METHODS
  A systematic literature search of MEDLINE, EMBASE, CENTRAL, and Web of Science databases using predefined search terms for relevant articles in any language.
  
  
  METHODS
  Randomised controlled trials and non-randomised studies reporting adjusted effect estimates were included. Summary estimates of the risks ratios (RRs) with therapy were calculated using a random-effect model. Outcomes evaluated were combined major adverse cardiovascular events (MACE) and major bleedings. Results Seven studies met the inclusion criteria and included 25,383 patients. A 600mg clopidogrel loading was associated with a 34% relative risk reduction of MACE (RR=0.66; 95% confidence intervals CI=0.52-0.84; p<0.001). Sub-analysis revealed a 47% risk reduction of MACE in randomised trials (RR=0.53; 95%CI=0.32-0.88; p=0.01) and a 31% relative risk reduction in non-randomised trials (RR=0.69; 95%CI=0.54-0.90; p=0.005) in patients receiving 600mg loading with clopidogrel. In patients suffering from acute coronary syndrome, 600mg clopidogrel loading was associated with a 24% relative risk reduction in MACE (RR=0.76; 95%CI=0.60-0.95; p=0.02). Importantly, the 600mg clopidogrel loading dose was not associated with an increased risk of major bleedings (RR=0.91; 95%CI=0.73-1.15; p=0.44).
  
  
  CONCLUSIONS
  This meta-analysis demonstrates that intensified clopidogrel loading with 600mg reduces the rate of major cardiovascular events without increase in major bleeding compared to 300mg in patients undergoing PCI during one month follow-up.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
authors.forename: Jolanta M
authors.initials: JM
authors.lastname: Siller-Matula
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.forename: Günter
authors.initials: G
authors.lastname: Christ
authors.forename: Karsten
authors.initials: K
authors.lastname: Schrör
authors.forename: Jacek
authors.initials: J
authors.lastname: Kubica
authors.forename: Harald
authors.initials: H
authors.lastname: Herkner
authors.forename: Bernd
authors.initials: B
authors.lastname: Jilma
mesh_terms: D054058:Acute Coronary Syndrome / Q000628:therapy*; D015906:Angioplasty, Balloon, Coronary / Q000379:methods*; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D009203:Myocardial Infarction / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D012680:Sensitivity and Specificity; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine