JACC: 600 mg loading dose of clopidogrel safe, effective for STEMI patients

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Pre-treating STEMI patients waiting to undergo PCI with a 600 mg loading dose of clopidogrel is safe and effective compared with a 300 mg loading dose, according to a study published in the Oct. 4 issue of the Journal of the American College of Cardiology.

“Given the high thrombotic risk of patients with STEMI, greater platelet inhibition may improve outcome in those patients receiving percutaneous coronary intervention (PCI),” Giuseppe Patti, MD, of the Campus Bio-Medico University, Rome, and colleagues wrote.

To better understand whether pre-treating STEMI patients with a 600 mg clopidogrel dose was more effective, Patti and colleagues conducted the ARMYDA-6 MI (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Myocardial Infarction) trial to compare the outcomes of a 600- and 300-mg loading dose of clopidogrel (Plavix, Sanofi-Aventis, Bristol Myers) in STEMI patients. To do so, Patti et al enrolled 201 patients undergoing primary PCI for STEMI. Of the 201 patients, 103 received a 600 mg loading dose of clopidogrel and 98 patients received a 300 mg loading dose of clopidogrel prior to the procedure.

The researchers used infarct size, defined as the area under the curve (AUC), as the study’s primary endpoint.

Patti et al reported infarct sizes to be significantly lower in patients receiving the higher dose of clopidogrel compared with those who received the lower dose. For the patients who received the 600-mg loading dose, median creatine kinase-myocardial band levels were 2,070 ng/ml vs. 3,049 ng/ml for patients who received the 300-mg dose.

The authors also reported that having a thrombolysis in MI flow grade less than three post-PCI was less frequent in the 600 mg arm compared with the 300 mg arm, 5.8 percent vs. 16.3 percent. Left ventricular ejection fraction (LVEF) at discharge was also improved in the 600 mg arm compared with the 300 mg dose arm, 52.1 percent vs. 48.8 percent. Also, fewer 30-day major adverse cardiovascular events occurred in patients who received the 600-mg dose compared with the 300 mg dose, 5.8 percent vs. 15 percent.

“There is a strong rationale for using an 'aggressive' antiplatelet strategy in patients with STEMI undergoing primary PCI; in fact, the time from administration of antiplatelet drugs to intervention is reduced in those patients, and there is increased platelet activation, which may limit the effects of antiplatelet agents, especially at standard doses,” Patti and colleagues offered.

“Use of newer, more potent antiplatelet drugs (e.g., prasugrel, ticagrelor) instead of clopidogrel significantly decreased the incidence of ischemic events in patients with acute coronary syndromes undergoing PCI, also including those with STEMI, but at the price of increased bleeding events, which may in turn worsen the prognosis,” the authors suggested. However, the researchers noted that a comparison of outcomes with prasugrel and pre-treatment with a 600 mg dose of clopidogrel has never been undertaken.

The authors found that a 600 mg loading dose of clopidogrel led to faster antiplatelet effects compared with the 300 mg dose. Additionally, Patti et al noted that the higher dose reduced the rate of nonresponders to the drug from 28 percent to 8 percent.

“When PCI is performed very early after clopidogrel administration, as typically occurs in the setting of STEMI (a mean of 36 minutes in our study), pre-treatment with a 600-mg loading dose allows stronger platelet inhibition at the time of the procedure,” the authors noted. “This may translate into a reduction of the thrombotic burden, reduced platelet-related intraprocedural events, decreased reperfusion injury, and subsequent reduction of the infarct size; the latter in ARMYDA-6 MI was paralleled by improved left ventricular function at discharge.

“ARMYDA-6 MI demonstrates that a 600 mg clopidogrel loading dose is safe and more effective than the 300 mg regimen in the context of primary PCI for STEMI,” Patti et al concluded.