title: Randomized trial comparing 600- with 300-mg loading dose of clopidogrel in patients with non-ST elevation acute coronary syndrome undergoing percutaneous coronary intervention: results of the Platelet Responsiveness to Aspirin and Clopidogrel and Troponin Increment after Coronary intervention in Acute coronary Lesions (PRACTICAL) Trial.
abstract: BACKGROUND
  There is uncertainty about the benefit of a higher loading dose (LD) of clopidogrel in patients with non-ST elevation acute coronary syndrome (NSTEACS) undergoing early percutaneous coronary intervention (PCI).
  
  
  METHODS
  We compared the effects of a 600- versus a 300-mg LD of clopidogrel on inhibition of platelet aggregation, myonecrosis, and clinical outcomes in patients with NSTEACS undergoing an early invasive management strategy. Patients with NSTEACS (n = 256, mean age 63 years, 81.6% elevated troponin) without thienopyridine for at least 7 days were randomized to receive 600- or 300-mg LD of clopidogrel. Percutaneous coronary intervention was performed in 140 patients, with glycoprotein IIb/IIIa inhibitor use in 68.6%. Adenosine diphosphate (ADP)-induced platelet aggregation was measured by optical platelet aggregometry immediately before coronary angiography.
  
  
  RESULTS
  Post-PCI myonecrosis was defined as a next-day troponin I greater than 5 times the upper limit of reference range and greater than baseline levels. Clopidogrel 600-mg LD compared with 300-mg LD was associated with significantly reduced ADP-induced platelet aggregation (49.7% vs 55.7% with ADP 20 micromol/L) but did not reduce post-PCI myonecrosis or adverse clinical outcomes to 6 months. There was no association between preprocedural platelet aggregation and outcome.
  
  
  CONCLUSIONS
  These data confirm a modest incremental antiplatelet effect of a 600-mg clopidogrel LD compared with 300-mg LD but provide no support for a clinical benefit in patients with NSTEACS managed with an early invasive strategy including a high rate (69%) of glycoprotein IIb/IIIa inhibitor use during PCI.
authors.affiliation: Royal Perth Hospital, Perth, Western Australia, Australia.
authors.forename: Gerald
authors.initials: G
authors.lastname: Yong
authors.forename: Jamie
authors.initials: J
authors.lastname: Rankin
authors.forename: Louise
authors.initials: L
authors.lastname: Ferguson
authors.forename: Jim
authors.initials: J
authors.lastname: Thom
authors.forename: John
authors.initials: J
authors.lastname: French
authors.forename: David
authors.initials: D
authors.lastname: Brieger
authors.forename: Derek P
authors.initials: DP
authors.lastname: Chew
authors.forename: Ron
authors.initials: R
authors.lastname: Dick
authors.forename: David
authors.initials: D
authors.lastname: Eccleston
authors.forename: Bernard
authors.initials: B
authors.lastname: Hockings
authors.forename: Darren
authors.initials: D
authors.lastname: Walters
authors.forename: Alan
authors.initials: A
authors.lastname: Whelan
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000628:therapy*; D015906:Angioplasty, Balloon, Coronary; D001241:Aspirin / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014336:Troponin / Q000097:blood
chemical_list: D010975:Platelet Aggregation Inhibitors; D014336:Troponin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin