Clopidogrel Versus Aspirin Monotherapy According to Atherothrombotic Risk Profile

BACKGROUND: Clopidogrel monotherapy has shown superior efficacy compared with aspirin after completion of dual antiplatelet therapy following percutaneous coronary intervention (PCI). However, whether treatment effects differ according to overall atherothrombotic risk integrating clinical and angiographic factors remains unclear. METHODS: This post hoc analysis 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) randomized trial included patients who completed guideline-directed dual antiplatelet therapy after PCI. Atherothrombotic risk was defined using the a Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention and complex PCI. Patients with Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention ≥3 or complex PCI were classified as higher risk, and those with a Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention <3 without complex PCI were classified as lower risk. The primary end point was major adverse cardiac and cerebrovascular events (death, myocardial infarction, or stroke). Bleeding was defined as Bleeding Academic Research Consortium type 2, 3, or 5. RESULTS: Among 5506 patients, 4486 (81.5%) were at higher risk and 1020 (18.5%) were at lower risk. Over a median 2.3 years, the incidence of major adverse cardiac and cerebrovascular events was higher in the higher-risk group (6.1% versus 3.1%; hazard ratio, 1.83 [95% CI, 1.17–2.78]; P =0.007). In higher-risk patients, clopidogrel reduced major adverse cardiac and cerebrovascular events compared with aspirin (4.6% versus 7.4%; hazard ratio, 0.67 [95% CI, 0.50–0.89]; P =0.006), with no difference in lower-risk patients (3.0% versus 3.2%; hazard ratio, 1.03; P =0.945; interaction P =0.242). Bleeding was similar between groups. CONCLUSIONS: After completion of dual antiplatelet therapy following PCI, clopidogrel monotherapy was associated with lower ischemic risk than aspirin in patients with higher atherothrombotic risk, without increased bleeding. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04418479.

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Journal
Circulation Cardiovascular Interventions
Published
2026-10-29
DOI
https://doi.org/10.1161/circinterventions.126.017277
Primary Topic
Antiplatelet Therapy and Cardiovascular Diseases
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article
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article

Clopidogrel Versus Aspirin Monotherapy According to Atherothrombotic Risk Profile

Joo Myung Lee, Ki Hong Choi, Danbee Kang, Seung‐Hyuk Choi et al.
5 links
Circulation Cardiovascular Interventions
Antiplatelet Therapy and Cardiovascular Diseases
article

Clopidogrel Versus Aspirin Monotherapy According to Atherothrombotic Risk Profile

Joo Myung Lee, Ki Hong Choi, Danbee Kang, Seung‐Hyuk Choi, Kyeong Ho Yun, Kiyuk Chang, Joon‐Hyung Doh, Jang Hyun Cho, Jeong Hoon Yang, Ung Kim, Doo Soo Jeon, Weon Kim, Young Bin Song, Cheol Whan Lee, Han Cheol Lee, Seung Hwan Han, Sung Gyun Ahn, Hyeon‐Cheol Gwon, Byung Ryul Cho, Chan Joon Kim, Seung‐Woon Rha, Taek Kyu Park, Jin‐Ok Jeong, Mahn‐Won Park, Ji Woong Roh, Jang‐Whan Bae, Joo‐Yong Hahn, Sung‐Ho Her, Dong Hyun Gim, Jong‐Young Lee, Hyun‐Jong Lee, Jin Bae Lee, Young Joon Hong, Doo‐Il Kim, Soo-Youn Lee, on behalf of the SMART-CHOICE 3 Investigators, Yong Hwan Park
article en

Abstract

BACKGROUND: Clopidogrel monotherapy has shown superior efficacy compared with aspirin after completion of dual antiplatelet therapy following percutaneous coronary intervention (PCI). However, whether treatment effects differ according to overall atherothrombotic risk integrating clinical and angiographic factors remains unclear. METHODS: This post hoc analysis 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) randomized trial included patients who completed guideline-directed dual antiplatelet therapy after PCI. Atherothrombotic risk was defined using the a Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention and complex PCI. Patients with Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention ≥3 or complex PCI were classified as higher risk, and those with a Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention <3 without complex PCI were classified as lower risk. The primary end point was major adverse cardiac and cerebrovascular events (death, myocardial infarction, or stroke). Bleeding was defined as Bleeding Academic Research Consortium type 2, 3, or 5. RESULTS: Among 5506 patients, 4486 (81.5%) were at higher risk and 1020 (18.5%) were at lower risk. Over a median 2.3 years, the incidence of major adverse cardiac and cerebrovascular events was higher in the higher-risk group (6.1% versus 3.1%; hazard ratio, 1.83 [95% CI, 1.17–2.78]; P =0.007). In higher-risk patients, clopidogrel reduced major adverse cardiac and cerebrovascular events compared with aspirin (4.6% versus 7.4%; hazard ratio, 0.67 [95% CI, 0.50–0.89]; P =0.006), with no difference in lower-risk patients (3.0% versus 3.2%; hazard ratio, 1.03; P =0.945; interaction P =0.242). Bleeding was similar between groups. CONCLUSIONS: After completion of dual antiplatelet therapy following PCI, clopidogrel monotherapy was associated with lower ischemic risk than aspirin in patients with higher atherothrombotic risk, without increased bleeding. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04418479.

Circulation Cardiovascular Interventions
Chonnam National University (KR), Chungbuk National University (KR), Yonsei University (KR), Chungnam National University (KR), Asan Medical Center (KR), Samsung Medical Center (KR), Kyung Hee University (KR), University of Ulsan (KR), Gachon University Gil Medical Center (KR), The Catholic University of Korea St. Vincent's Hospital (KR), Wonkwang University Hospital (KR), The Catholic University of Korea Incheon St. Mary's Hospital (KR), Inje University Haeundae Paik Hospital (KR), Wonju Severance Christian Hospital (KR), Kangbuk Samsung Hospital (KR), The Catholic University of Korea Uijeongbu St. Mary's Hospital (KR), Inje University Ilsan Paik Hospital (KR), Kangwon National University Hospital (KR), The Catholic University of Korea Daejeon St. Mary's Hospital (KR), Kyung Hee University Medical Center (KR), Sejong General Hospital (KR), The Catholic University of Korea Bucheon St. Mary's Hospital (KR), Chungnam National University Hospital (KR), Yeungnam University Medical Center (KR), The Catholic University of Korea Seoul St. Mary's Hospital (KR), Chungbuk National University Hospital (KR), Samsung Changwon Hospital (KR), Korea University Guro Hospital (KR), Sungkyunkwan University (KR), Catholic University of Korea (KR)
Good health and well-being
Openalex Percentile: Top 11%
Antiplatelet Therapy and Cardiovascular Diseases
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