MedWire News: A 600 mg loading dose of clopidogrel before percutaneous coronary intervention (PCI) reduces myocardial infarct size and improves myocardial salvage compared with a 300 mg loading dose, say researchers.
"To the best of our knowledge, this is the first study to demonstrate the superior efficacy of a 600 mg clopidogrel loading dose compared with that of a 300 mg dose in terms of infarct size reduction, the extent of microvascular obstruction, and myocardial salvage using cardiovascular magnetic resonance imaging (MRI)," comment Joo-Yong Hahn (Sungkyunkwan University School of Medicine, Seoul, Korea) and team.
The American Heart Journal study involved 198 patients who underwent primary PCI for ST-segment elevation myocardial infarction (STEMI). All patients received dual oral antiplatelet therapy with aspirin 300 mg and clopidogrel 300 mg (n=81) or 600 mg (n=117) before PCI.
The findings revealed that the median infarct size, which was assessed with delayed-enhancement imaging, was significantly smaller in the 600 mg group than in the 300 mg group, at 17.3% versus 21.7% (p=0.03).
Myocardial salvage index, which was calculated using the area at risk (quantified on T2-weighted images), was greater in the 600 mg group than in the 300 mg index, at 47.7 versus 32.0 (p<0.01).
Patients who received a 600 mg loading dose of clopidogrel also had significantly less microvascular obstruction, and a smaller number of segments with more than 75% of infarct transmurality than those who received 300 mg.
Multivariate analysis demonstrated that the use of a 600 mg loading dose of clopidogrel reduced the risk for a large infarct (percent infarct volume >18.5% of median infarct size) by 47%.
The associations between loading dose and infarct size, myocardial salvage index, and number of segments with more than 75% of infarct transmurality were still significant after propensity-score matching.
The authors say that pretreatment with clopidogrel has become the standard treatment for patients undergoing PCI because clopidogrel is an inactive drug and needs to be metabolized after oral administration, which results in a delayed onset of action.
However, at least 6 hours are required after a 300 mg dose for sufficient platelet inhibition and reduction of adverse cardiac events, they say. Therefore, they propose that a 600 mg dose could provide "more potent and quicker platelet inhibition."
"Our findings may explain the previously documented improved clinical outcomes after a 600 mg loading dose of clopidogrel," they conclude.
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