NEW YORK (Reuters Health) – Pretreatment with a 600-mg versus a standard 300-mg loading dose of clopidogrel in the setting of urgent percutaneous coronary intervention for ST-segment elevated MI (STEMI) is associated with smaller infarct size and other benefits, according to a multicenter European study.

“The results provide a randomized contribution supporting the use of 600 mg clopidogrel as the loading dose of choice in these patients,” conclude the authors of the report in the October 4 issue of the Journal of the American College of Cardiology.

Dr. Giuseppe Patti, at the Campus Bio-Medico University in Rome, Italy, and colleagues note that the antiplatelet adequacy of the standard starting dose of clopidogrel in MI patients undergoing PCI is a matter of debate.

For example, a recent Korean study found that doubling the standard 300-mg loading dose conferred no benefit (see Reuters Health report on January 26, 2011, “Standard clopidogrel loading dose OK in Asian STEMI patients undergoing PCI”). On the other hand, observational studies in Western populations do suggest that 600-mg improves outcomes of STEMI treated with primary PCI — but this has not been evaluated in a randomized prospective trial.

Hence, the authors undertook such a study in 201 patients undergoing PCI for STEMI, who were randomly assigned to receive a 600-mg or 300-mg loading dose of clopidogrel before the procedure.

Infarct size was significantly smaller with the higher than the standard clopidogrel dose, based on CK-MB levels (2070 vs 3049 ng/mL; p=0.0001) and troponin-I levels (255 vs 380 ng/ml; p<0.0001), the investigators found.

Furthermore, left ventricular ejection fraction at discharge was improved (52.1% vs. 48.8%; p= 0.026) and major adverse cardiovascular events at 30 days were fewer (5.8% vs. 15%; p=0.049) with the higher verus lower dose.

Regarding safety, bleeding and complications at the access site were not increased with the higher clopidogrel dose, according to the report.

However, further studies are needed to determine the effect of the higher dose on survival, Dr. Patti and colleagues comment.

In discussing the results, they note that prasugrel and ticagrelor have been shown to reduce ischemic events more than clopidogrel in patients with ACS undergoing PCI, but with increased bleeding events.

They conclude, “Our results may have relevance with regard to practice patterns because clopidogrel is nevertheless still widely used in those patients, especially in the presence of high bleeding risk features, such as bleeding-prone gastrointestinal or genitourinary lesions, older age, low body weight, and previous stroke.”

Reference:
Outcome Comparison of 600- and 300-mg Loading Doses of Clopidogrel in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: Results From the ARMYDA-6 MI (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Myocardial Infarction) Randomized Study
J Am Coll Cardiol 2011;58:1592–1599.