SMart Angioplasty Research Team: CHoice of Optimal Anti-Thrombotic Strategy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents 3

Study Overview
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Brief Summary
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This study is prospective, open-label, two-arm, randomized multicenter trial to evaluate the efficacy and safety of clopidogrel monotherapy as compared with aspirin monotherapy beyond 12 months after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in patients being treated with dual antiplatelet therapy (DAPT) at high risk for recurrent ischemic events.

Detailed Description
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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 as compared with aspirin monotherapy beyond 12 months after PCI with current-generation DES in patients being treated with DAPT at high risk for recurrent ischemic events.

Official Title
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Clopidogrel Versus Aspirin Monotherapy Beyond Twelve Months After Percutaneous Coronary Intervention in Patients at High Risk for Recurrent Ischemic Events

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Aspirin
* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: i) Subject must be at least 19 years of age ii) Subject who is able to understand risks, benefits and treatment alternatives and sign informed consent voluntarily. iii) Patients being treated with DAPT at high risk for recurrent ischemic events* who underwent PCI at least 12 months ago. *High risk for recurrent ischemic events was defined as one or more of the following clinical or lesion characteristics. A. Clinical characteristics Patients presented with acute myocardial infarction. Patients with diabetes mellitus who receiving oral hypoglycemic agent or insulin. B. Complex lesion characteristics** **Complex lesion was defined as one or more of the following. True bifurcation lesion (Medina 1,1,1/1,0,1/0,1,1) and is able to assess the side branch ostium Chronic total occlusion (≥3 months) as target lesion PCI for unprotected left main disease (left main ostium, body, or distal bifurcation including non-true bifurcation lesions) Long coronary lesions (implanted stent length ≥38 mm) Multi-vessel PCI (≥ 2 vessels treated at one PCI session) Multiple stent needed (≥ 3 stents per patient) In-stent restenosis lesion as target lesion Severely calcified lesion (encircling calcium in angiography) Ostial lesions of left anterior descending artery, left circumflex artery, or right coronary artery Exclusion Criteria: i) Known hypersensitivity or contraindications to study medications (aspirin or clopidogrel) ii) Patients taking warfarin or non-vitamin K antagonist (dabigatran, rivaroxaban, edoxaban, or apixaban) iii) Patients who require DAPT due to atherosclerotic disease other than coronary artery disease iv) Patients who are scheduled for revascularization treatment of coronary artery v) Pregnant or lactating women vi) 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)

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, open-label, two-arm, randomized controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aspirin monotherapy arm<br>Patients will receive 100 mg of aspirin once daily. | Drug: Aspirin<br>* Randomization will be performed 1:1 between clopidogrel and aspirin monotherapy in patients being treated with dual antiplatelet therapy (DAPT) at high risk for recurrent ischemic events who have been over 12 months after percutaneous coronary intervention (PCI) with drug-eluting stent (DES). This group will be taken aspirin 100 mg once daily during the study period.<br>|
| Experimental: Clopidogrel monotherapy arm<br>Patients will receive 75 mg of clopidogrel once daily. | Drug: Clopidogrel<br>* Randomization will be performed 1:1 between clopidogrel and aspirin monotherapy in patients being treated with dual antiplatelet therapy (DAPT) at high risk for recurrent ischemic events who have been over 12 months after percutaneous coronary intervention (PCI) with drug-eluting stent (DES). This group will be taken clopidogrel 75 mg once daily during the study period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of major adverse cardiac and cerebrovascular event (MACCE) | a composite of all-cause death, myocardial infarction, or stroke | 1-year after last patient enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of all-cause death | Death by any cause | 1-year after last patient enrollment | 
| Rates of cardiac death | Death by cardiac cause | 1-year after last patient enrollment | 
| Rates of myocardial infarction | Myocardial infarction | 1-year after last patient enrollment | 
| Rates of stroke | Stroke | 1-year after last patient enrollment | 
| Rates of stent thrombosis | definite or probable by Academic Research Consortium [ARC] definition | 1-year after last patient enrollment | 
| Rates of all-cause death or MI | A composite of all-cause death or MI | 1-year after last patient enrollment | 
| Rates of cardiac death or MI | A composite of cardiac death or MI | 1-year after last patient enrollment | 
| Rates of cardiac death, MI, or stroke | A composite of cardiac death, MI, or stroke | 1-year after last patient enrollment | 
| Rates of cardiac death, MI, or stent thrombosis | A composite of cardiac death, MI, or stent thrombosis | 1-year after last patient enrollment | 
| Rates of major Bleeding | BARC [Bleeding Academic Research Consortium] types 3 or 5 | 1-year after last patient enrollment | 
| Rates of bleeding | BARC [Bleeding Academic Research Consortium] types 2, 3, or 5 | 1-year after last patient enrollment | 
| Rates of upper gastrointestinal clinical event | A composite of upper gastrointestinal clinical event | 1-year after last patient enrollment | 
| Rates of gastrointestinal ulcer or bleeding | A composite of gastrointestinal ulcer or bleeding | 1-year after last patient enrollment | 
| New diagnosed rates of gastroesophageal reflux disease (GERD) | Gastroesophageal reflux disease (GERD) | 1-year after last patient enrollment | 
| Rates of NACE (Net adverse clinical events) | MACCE + BARC type 3 or 5 bleeding | 1-year after last patient enrollment | 
| Rates of Target-lesion revascularization (TLR) | Target-lesion revascularization (TLR) | 1-year after last patient enrollment | 
| Rates of Target-vessel revascularization (TVR) | Target-vessel revascularization (TVR) | 1-year after last patient enrollment | 
| Rates of any revascularization | any revascularization including TLR, TVR, and non-TVR re-percutaneous coronary intervention | 1-year after last patient enrollment | 
| Medical cost | Medical cost | 1-year after last patient enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Percutaneous Coronary Intervention, Antiplatelet Therapy, Complex Coronary Lesion, Aspirin, Clopidogrel