title: Randomized trial of high loading dose of clopidogrel for reduction of periprocedural myocardial infarction in patients undergoing coronary intervention: results from the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) study.
abstract: BACKGROUND
  Aggressive platelet inhibition is crucial to reduce myocardial injury and early cardiac events after coronary intervention. Although observational data have suggested that pretreatment with a high loading dose of clopidogrel may be more effective than a conventional dose, this hypothesis has never been tested in a randomized trial.
  
  
  RESULTS
  A total of 255 patients scheduled to undergo percutaneous coronary intervention were randomized to a 600-mg (n=126) or 300-mg (n=129) loading regimen of clopidogrel given 4 to 8 hours before the procedure. Creatine kinase MB, troponin I, and myoglobin levels were measured at baseline and at 8 and 24 hours after intervention. The primary end point was the 30-day occurrence of death, myocardial infarction (MI), or target vessel revascularization. The primary end point occurred in 4% of patients in the high loading dose versus 12% of those in the conventional loading dose group (P=0.041) and was due entirely to periprocedural MI. Peak values of all markers were significantly lower in patients treated with the 600-mg regimen (P< or =0.038). Safety end points were similar in the 2 arms. At multivariable analysis, the high loading regimen was associated with a 50% risk reduction of MI (OR 0.48, 95% CI 0.15 to 0.97, P=0.044). An incremental benefit was observed in patients randomized to the 600-mg dose who were receiving statins, with an 80% risk reduction.
  
  
  CONCLUSIONS
  Pretreatment with a 600-mg loading dose of clopidogrel 4 to 8 hours before the procedure is safe and, as compared with the conventional 300-mg dose, significantly reduced periprocedural MI in patients undergoing percutaneous coronary intervention. These results may influence practice patterns with regard to antiplatelet therapy before percutaneous revascularization.
authors.affiliation: Department of Cardiovascular Sciences, Campus Bio-Medico University, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Patti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Colonna
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pasceri
authors.forename: Leonardo Lassandro
authors.initials: LL
authors.lastname: Pepe
authors.forename: Antonio
authors.initials: A
authors.lastname: Montinaro
authors.forename: Germano
authors.initials: G
authors.lastname: Di Sciascio
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects* / Q000379:methods; D015415:Biomarkers / Q000032:analysis; D000077144:Clopidogrel; D003402:Creatine Kinase / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control*; D009204:Myocardial Revascularization / Q000009:adverse effects; D009211:Myoglobin / Q000032:analysis; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011292:Premedication; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019210:Troponin I / Q000032:analysis
chemical_list: D015415:Biomarkers; D009211:Myoglobin; D010975:Platelet Aggregation Inhibitors; D019210:Troponin I; D000077144:Clopidogrel; D003402:Creatine Kinase; D013988:Ticlopidine