Department of Cardiovascular Sciences， Campus Bio-Medico University， Rome， Italy.

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.