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600-mg loading dose of clopidogrel reduced infarct size in STEMI patients
Patti G. J Am Coll Cardiol. 2011;58:1592-1599.
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A reduction of infarct size and improvement of angiographic results, residual cardiac function and 30-day major adverse CV events were associated with pretreatment with a 600-mg loading dose of clopidogrel vs. a 300-mg loading dose before primary percutaneous coronary intervention in STEMI patients, according to an analysis of the ARMYDA-6 MI study.
Patients with STEMI undergoing primary PCI were enrolled in the study. Researchers randomly assigned a 600-mg or 300-mg loading dose of clopidogrel to patients before the procedure. The primary endpoint was defined as the evaluation of infarct size, and secondary endpoints were the prevalence of thrombolysis in MI flow grade of more than 1 before PCI and less than 3 after PCI; left ventricular ejection fraction by transthoracic echocardiography at discharge; incidence of major adverse CV events at 30 days; and occurrence of bleeding or entry site complications.
Overall, the primary endpoint concluded that infarct size was lower in patients assigned to the 600-mg dose. Looking at secondary endpoints, TIMI flow grade of more than 1 at diagnostic coronary angiography before PCI was found in 21.4% of patients in the 600-mg arm vs. 12.2% in the 300-mg arm, whereas a lower incidence of TIMI flow grade of less than 3 was associated with the 600-mg dose (P=.031). Study results showed that LVEF early after PCI was similar in the two arms (P=.42), but was higher in the 600-mg dose at discharge (P=.026). The 600-mg group also had a reduced incidence of 30-day major adverse CV events vs. the 300-mg group (P=.049).
Researchers also found that symptom-to-balloon (P=.86) time and clopidogrel load-to-balloon time (P=.45) were similar in the two arms.
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The results are somewhat limited by a small sample, but having said that, they are significant. Furthermore while 600 mg improved non fatal outcomes, the important fact was the benefit was achieved without an increase in bleeding or other measured side effect. Furthermore, there appears to be a finite number of receptors bound by a P2Y12 inhibiter so increasing the dosage improves the possibility of achieving an important therapeutic level early while not paying a price for the higher loading dose.
George Vetrovec, MD
Cardiology
Today Editorial Board member
Disclosures: Dr. Vetrovec is a speaker and consultant for Lilly and Daiichi Sanyko.
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