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

Study Questions:

How does the safety and efficacy of clopidogrel loading dose of 300 versus 600 mg compare in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI)?

Methods:

The ARMYDA-6 MI trial authors randomized 201 patients undergoing primary PCI for STEMI to 600 mg (n = 103) or 300 mg (n = 98) clopidogrel loading dose before the procedure. The primary endpoint was the evaluation of the infarct size, defined as area under the curve of cardiac markers.

Results:

There was no difference in infarct localization or symptom-to-balloon time between the two groups. Infarct size was significantly lower in the high-dose regimen (median creatine kinase-myocardial band 2,070 ng/ml vs. 3,049 ng/ml in the 300 mg group, p < 0.0001; troponin I 255 ng/ml vs. 380 ng/ml, p < 0.0001). The post-PCI Thrombolysis in Myocardial Infarction flow <3 after PCI was more frequent (5.8% vs. 16.3%, p = 0.031) in the higher-dose group. The higher loading dose arm had higher left ventricular ejection fraction at discharge (52.1% vs. 48.8, p = 0.026) and a lower incidence of 30-day major adverse cardiovascular events (5.8% vs. 15%, p = 0.049). There was no difference in bleeding or access site complications between the two arms.

Conclusions:

Compared with a 300 mg loading dose of clopidogrel, a 600 mg loading dose is associated with a better outcome in patients undergoing primary PCI.

Perspective:

This study corroborates the common practice of using a higher loading dose of clopidogrel in patients undergoing primary PCI, although an increasing number of these patients are being treated with prasugrel. The results of this small randomized, controlled study are similar to the post hoc analysis from the HORIZONS trial (Dangas et al., J Am Coll Cardiol 2009;54:1438-46), and suggest that the higher loading dose of clopidogrel should be used in patients undergoing primary PCI.

Keywords: Myocardial Infarction, Platelet Aggregation Inhibitors, Ventricular Function, Left, Thiophenes, Creatine Kinase, MB Form, Piperazines, Angioplasty, Percutaneous Coronary Intervention, Incidence, Coronary Angiography, Troponin I, Cardiovascular Diseases, Stroke Volume, Nucleic Acid Conformation


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