SMart Angioplasty Research Team: CHoice of Optimal Anti-Thrombotic Strategy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents 3 (SMART-CHOICE3)

Clopidogrel Versus Aspirin Monotherapy After Percutaneous Coronary Intervention and Standard Dual Antiplatelet Therapy in Patients At High Risk for Recurrent Ischemic Events

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Aspirin; Drug: Clopidogrel

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 5506
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aspirin monotherapy arm; Patients will receive 100 mg of aspirin once daily.	Drug: Aspirin; Randomization will be performed 1:1 between clopidogrel and aspirin monotherapy in patients who completed standard duration of dual antiplatelet therapy (DAPT) and who were at high risk for recurrent ischemic events after percutaneous coronary intervention (PCI) with drug-eluting stent (DES). This group will be taken aspirin 100 mg once daily during the study period.; Other Names: Aspirin monotherapy
Experimental: Clopidogrel monotherapy arm; Patients will receive 75 mg of clopidogrel once daily.	Drug: Clopidogrel; Randomization will be performed 1:1 between clopidogrel and aspirin monotherapy in patients who completed standard duration of dual antiplatelet therapy (DAPT) and who were at high risk for recurrent ischemic events after percutaneous coronary intervention (PCI) with drug-eluting stent (DES). This group will be taken clopidogrel 75 mg once daily during the study period.; Other Names: Clopidogrel monotherapy

What is the study measuring?

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 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 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
Rates of cardiovascular death	Death by cardiovascular cause	1-year after last patient enrollment
Rates of cardiovascular death or MI	A composite of cardiovascular death or MI	1-year after last patient enrollment
Rates of cardiovascular death, MI, or stroke	A composite of cardiovascular death, MI, or stroke	1-year after last patient enrollment
Rates of cardiovascular death, MI, or stent thrombosis	A composite of cardiovascular death, MI, or stent thrombosis	1-year after last patient enrollment

Collaborators and Investigators

• Sponsor: Joo-Yong Hahn
• Investigators: Study Chair: Joo-Yong Hahn, MD, PhD, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2020
• Primary Completion (Actual): October 31, 2024
• Study Completion (Actual): November 12, 2024

Study Registration Dates

• First Submitted: June 1, 2020
• First Submitted That Met QC Criteria: June 2, 2020
• First Posted (Actual): June 5, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 29, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Aspirin; Percutaneous Coronary Intervention; Clopidogrel; Antiplatelet Therapy; Complex Coronary Lesion
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Coronary Artery Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrin Modulating Agents; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Neurotransmitter Agents; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel; Aspirin
• Other Study ID Numbers: CHOICE-3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No