The rationale for the use of a double dose of clopidogrel in the study of Mangiacapra et al for those with ST-segment elevation myocardial infarction (STEMI) who underwent primary coronary angioplasty was to rapidly suppress platelet activity to avoid subsequent cardiovascular ischemic events. As is known, other adjuvant antiplatelet therapy trials for patients with STEMI who undergo primary angioplasty have revealed similar results, with reductions of cardiovascular end points and events of acute and subacute instant thrombosis. However, additional benefits have been emphasized, especially for those with high risk profiles. For example, in the Korean Acute Myocardial Infarction Registry, Chen et al pointed out that cilostazol-based triple therapy should be used for elderly, female, and diabetic patients with STEMI for primary angioplasty. De Luca et al performed a meta-regression analysis of randomized trials and demonstrated a mortality benefit proportional to baseline risk in abciximab-adjuvant triple therapy. In the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, Dangas et al reported that Killip class I had the lowest hazard ratio (0.36), and a clopidogrel loading dose of 600 mg had a hazard ratio of 0.67 for the occurrence of cardiovascular events at 30 days after percutaneous coronary intervention, implying that the benefits of a higher loading dose of clopidogrel will be blunted in the condition of Killip class I.

Recently, Pocock et al reported that the highest death rate from ischemia occurred on days 0 and 1 (hazard ratio 15.57), but the highest death rate from major bleeding occurred during days 8 to 30 (hazard ratio 4.80) after primary angioplasty. This finding is consistent with the results of the Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent Events/Optimal Antiplatelet Strategy for Interventions (CURRENT-OASIS 7) trial that clopidogrel 600 mg/day can be safely used for 1 week without increasing the rate of major bleeding. Accordingly, the use of a 600-mg loading dose of clopidogrel should be recommended in patients with STEMI with high risk profiles for primary angioplasty. How to identify nonresponders to clopidogrel will be the next major issue for those who require a loading dose of clopidogrel >600 mg for primary angioplasty.