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

Circulation. 2005 Apr 26;111(16):2099-106. doi: 10.1161/01.CIR.0000161383.06692.D4. Epub 2005 Mar 6.

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.

Methods and 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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Angioplasty, Balloon, Coronary / adverse effects*
  • Angioplasty, Balloon, Coronary / methods
  • Biomarkers / analysis
  • Clopidogrel
  • Creatine Kinase / analysis
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / prevention & control*
  • Myocardial Revascularization / adverse effects
  • Myoglobin / analysis
  • Platelet Aggregation Inhibitors / therapeutic use
  • Premedication*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Troponin I / analysis

Substances

  • Biomarkers
  • Myoglobin
  • Platelet Aggregation Inhibitors
  • Troponin I
  • Clopidogrel
  • Creatine Kinase
  • Ticlopidine