Background-Whether triple antiplatelet therapy is superior or similar to dual antiplatelet therapy in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention in the era of drug-eluting stents remains unclear. Methods and Results-A total of 4203 ST-segment elevation myocardial infarction patients who underwent primary percutaneous coronary intervention with drug-eluting stents were analyzed retrospectively in the Korean Acute Myocardial Infarction Registry (KAMIR). They received either dual (aspirin plus clopidogrel; dual group; nϭ2569) or triple (aspirin plus clopidogrel plus cilostazol; triple group; nϭ1634) antiplatelet therapy. The triple group received additional cilostazol at least for 1 month. Various major adverse cardiac events at 8 months were compared between these 2 groups. Compared with the dual group, the triple group had a similar incidence of major bleeding events but a significantly lower incidence of in-hospital mortality. Clinical outcomes at 8 months showed that the triple group had significantly lower incidences of cardiac death (adjusted odds ratio, 0.52; 95% confidence interval, 0.32 to 0.84; Pϭ0.007), total death (adjusted odds ratio, 0.60; 95% confidence interval, 0.41 to 0.89; Pϭ0.010), and total major adverse cardiac events (adjusted odds ratio, 0.74; 95% confidence interval, 0.58 to 0.95; Pϭ0.019) than the dual group. Subgroup analysis showed that older (Ͼ65 years old), female, and diabetic patients got more benefits from triple antiplatelet therapy than their counterparts who received dual antiplatelet therapy. Conclusions-Triple antiplatelet therapy seems to be superior to dual antiplatelet therapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with drug-eluting stents. These results may provide the rationale for the use of triple antiplatelet therapy in these patients. (Circulation. 2009;119:3207-3214.)

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1. Of the patients suffering from acute myocardial infarction (AMI), smokers are younger than non-smokers, which may be a major confounding factor causing 'smoker's paradox'. Therefore, in the present study we evaluated the 'smoker's paradox' in young patients with AMI.2. In all, 1218 young AMI patients (≤ 45 years of age), comprising 990 smokers and 228 non-smokers, were enrolled in the present study. In-hospital and 8 months clinical outcomes were compared between the smokers and non-smokers. 3. Baseline clinical characteristics showed that smokers were more likely to be male (97.9% vs 72.4%; P < 0.001) and had a higher rate of ST-segment elevation myocardial infarction (71.3% vs 59.5%; P = 0.001) than non-smokers. Clinical outcomes showed that smokers had lower rates of in-hospital cardiac death (0.8% vs 3.5%; P = 0.004), total death (0.8% vs 3.5%; P = 0.004) and 8 months cardiac death (1.1% vs 3.9%; P = 0.006) and total death (1.3% vs 4.4%; P = 0.005) than non-smokers. Multivariable logistic analysis showed that current smoking was an independent protective predictor of 8 months cardiac death (odds ratio (OR) 0.25; 95% confidence interval (CI) 0.07-0.92; P = 0.037) and total death (OR 0.26; 95% CI 0.09-0.82; P = 0.021). Subgroup analysis in patients who underwent percutaneous coronary intervention after AMI showed that current smoking was an independent protective predictor of 8 months total major adverse cardiac events (OR 0.47; 95% CI 0.23-0.97; P = 0.041). 4. Current smoking seems to be associated with better clinical outcomes in young patients with AMI, suggesting the existence of the 'smoker's paradox' in this particular subset of patients.