This study is a prospective, open-label, two-arm, randomized multicenter trial to compare the efficacy and safety of clopidogrel versus aspirin monotherapy beyond the standard duration of dual antiplatelet therapy (DAPT) (more than 12 months for myocardial infarction [MI] and more than 6 months for non-MI) after percutaneous coronary intervention (PCI) in patients at high risk of recurrent ischemic events.

After the introduction of the second-generation drug-eluting stents (DES), the rates of device-related failure or target lesion failure such as restenosis and stent thrombosis has been markedly decreased, compared with the era of bare-metal stents or first-generation DES. Nevertheless, the risk of ischemic events including very late stent thrombosis after percutaneous coronary intervention (PCI) has still remained even though the use of second-generation DES. In this regard, the ACC (American College of Cardiology)/AHA (American Heart Association) and ESC (European Society of Cardiology) guidelines recommended that dual antiplatelet therapy (DAPT) should be considered for 12 months or longer in patients presented with acute coronary syndrome (ACS) and for 6 months or longer in patients presented with stable ischemic heart disease (SIHD) after PCI with DES. In particular, patients presented with a high risk of ischemic events such as diabetes mellitus, myocardial infarction, or complex coronary lesions were associated with significantly increased future recurrent ischemic events after PCI with DES. In addition, maintenance of DAPT for 12 months or longer has been shown to reduce the recurrence of ischemic events up to 44% in patients treated with PCI for complex coronary artery lesion; therefore the current guideline recommended that prolonged DAPT might be considered when performing complex PCI. However, prolonged DAPT increases bleeding risk and cost. Endoscopic, dental, and surgical procedures are often delayed due to prolonged DAPT, which may affect the patient's quality of life. Therefore, to determine the optimal or minimal necessary duration of DAPT is very important.

The other important issue is that which antiplatelet agent is more appropriate after DAPT. Aspirin monotherapy has been recommended traditionally. However, there is no randomized comparison study between aspirin monotherapy versus clopidogrel monotherapy after DAPT in patients undergoing PCI with DES. Furthermore, clopidogrel is also actively used as a monotherapy after DAPT in real-world practice. In CAPRIE (clopidogrel versus aspirin in patients at risk of ischemic events) trial, clopidogrel showed a superior efficacy in preventing ischemic events compared with aspirin. Moreover, the incidence of gastrointestinal bleeding was significantly lower with clopidogrel than with aspirin. Clopidogrel monotherapy can reduce ischemic events and bleeding risk compared with aspirin monotherapy.

Therefore, the purpose of the SMART-CHOICE 3 (SMart Angioplasty Research Team: CHoice of Optimal Anti-Thrombotic Strategy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents 3) trial is to determine the efficacy and safety of clopidogrel monotherapy compared with aspirin monotherapy beyond the standard duration of DAPT after PCI with current-generation DES in patients at high risk for recurrent ischemic events.

Inclusion Criteria:

1. Subject must be at least 19 years of age

2. Patients at high risk of recurrence of ischemic events who have undergone PCI using a DES and are receiving standard DAPT (12 months* or more for myocardial infarction and 6 months* or more for non-myocardial infarction)

3. Patients at high risk for recurrent ischemic events, which were defined as one or more of the following clinical or lesion characteristics.

   A. Clinical characteristics

   1. Patients with prior myocardial infarction.
   2. Patients with diabetes mellitus who receive oral hypoglycemic agent or insulin.

   B. Complex lesion characteristics Complex lesion was defined as one or more of the following.

   1. True bifurcation lesion (Medina 1,1,1/1,0,1/0,1,1) and is able to assess the side branch ostium
   2. Chronic total occlusion (≥3 months) as target lesion
   3. PCI for unprotected left main disease (left main ostium, body, or distal bifurcation including non-true bifurcation lesions)
   4. Long coronary lesions (implanted stent length ≥38 mm)
   5. Multi-vessel PCI (≥ 2 vessels treated at one PCI session)
   6. Multiple stent needed (≥ 3 stents per patient)
   7. In-stent restenosis lesion as target lesion
   8. Severely calcified lesion (encircling calcium in angiography) i . Ostial lesions of left anterior descending artery, left circumflex artery, or right coronary artery

4. Subject who is able to understand risks, benefits and treatment alternatives and sign informed consent voluntarily.

Exclusion Criteria:

1. Known hypersensitivity or contraindications to study medications (aspirin or clopidogrel)
2. Patients who need continuous anticoagulant therapy.
3. Patients who require DAPT due to atherosclerotic disease other than coronary artery disease
4. Patients who are scheduled for revascularization treatment of coronary artery
5. A patient who are taking single antiplatelet therapy at screening
6. Pregnant or lactating women
7. Non-cardiac co-morbid conditions are present with life expectancy <2 year or that may result in protocol non-compliance (per site investigator's medical judgment)