Ki Hong Choi1, Yong Hwan Park2, Young Bin Song1, Taek Kyu Park1, Joo Myung Lee1, Jeong Hoon Yang1, Jin-Ho Choi1, Seung-Hyuk Choi1, Ju-Hyeon Oh2, Woo Jung Chun2, Woo Jin Jang3, Eul-Soon Im4, Jin-Ok Jeong5, Byung Ryul Cho6, Seok Kyu Oh7, Kyeong Ho Yun7, Deok-Kyu Cho8, Jong-Young Lee9, Young-Youp Koh10, Jang-Whan Bae11, Jae Woong Choi12, Wang Soo Lee13, Hyuck Jun Yoon14, Seung Uk Lee15, Jang Hyun Cho16, Woong Gil Choi17, Seung-Woon Rha18, Hyeon-Cheol Gwon1, Joo-Yong Hahn1. 1. Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 2. Department of Cardiology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea. 3. Department of Cardiology, Ewha Woman's University Seoul Hospital, Ewha Woman's University School of Medicine, Seoul, Korea. 4. Division of Cardiology, Dongsuwon General Hospital, Suwon, Korea. 5. Chungnam National University Hospital, Daejeon, Korea. 6. Division of Cardiology, Kangwon National University Hospital, Chuncheon, Korea. 7. Department of Cardiovascular Medicine, Regional Cardiocerebrovascular Center, Wonkwang University Hospital, Iksan, Korea. 8. Division of Cardiology, Department of Internal Medicine, Yongin Severance Hospital, Yongin, Korea. 9. Division of Cardiology, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea. 10. Department of Internal Medicine, Chosun University Hospital, Gwangju, Korea. 11. Department of Internal Medicine, College of Medicine, Chungbuk National University Hospital, Cheongju, Korea. 12. Eulji General Hospital, Seoul, Korea. 13. Chung-Ang University Hospital, Seoul, Korea. 14. Keimyung University Dongsan Medical Center, Daegu, Korea. 15. Kwangju Christian Hospital, Gwangju, Korea. 16. St Carollo Hospital, Suncheon, Korea. 17. Konkuk University Chungju Hospital, Chungju, Korea. 18. Korea University Guro Hospital, Seoul, Korea.
Abstract
Importance: Although P2Y12 inhibitor monotherapy after a minimum period of dual antiplatelet therapy (DAPT) is a well-known way to reduce the risk of bleeding after percutaneous coronary intervention (PCI), data comparing long-term clinical outcomes between P2Y12 inhibitor monotherapy and extended DAPT in patients undergoing PCI have been unavailable. Objective: To identify the long-term safety and efficacy of P2Y12 inhibitor monotherapy following 3 months of DAPT after PCI. Design, Setting, and Participants: The Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy and Dual Antiplatelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents (SMART-CHOICE) trial was an open-label, noninferiority, randomized clinical trial, enrolling patients who underwent PCI with drug-eluting stent at 33 hospitals in Korea from March 2014 through July 2017. Clinical follow-up was extended to 3 years and completed in August 2020. Interventions: Patients were randomly assigned to either P2Y12 inhibitor monotherapy after 3 months of DAPT or DAPT for 12 months or longer. Main Outcomes and Measures: The primary end point was major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) at 3 years. The secondary end points included the components of the primary end point, bleeding (defined as Bleeding Academic Research Consortium [BARC] types 2-5), and major bleeding (BARC types 3-5). Results: In total, 2993 patients were randomly assigned to receive P2Y12 inhibitor monotherapy after 3 months of DAPT (1495 patients [50%]; mean [SD] age, 64.6 [10.7] years; 1087 [72.7%] male) or prolonged DAPT (1498 patients [50%]; mean [SD] age, 64.6 [10.7] years; 1111 [74.2%] male) after PCI. At 3 years, the primary end point occurred in 87 individuals (6.3%) in the P2Y12 inhibitor monotherapy group and 83 (6.1%) in the prolonged DAPT group (hazard ratio [HR], 1.06 [95% CI, 0.79-1.44]; P = .69). P2Y12 inhibitor monotherapy significantly reduced the risk of bleeding (BARC types 2-5: 112 [3.2%] vs 44 [8.2%]; HR, 0.39 [95% CI, 0.28-0.55]; P < .001) and major bleeding (BARC types 3-5; 17 [1.2%] vs 31 [2.4%]; HR, 0.56 [95% CI, 0.31-0.99]; P = .048), compared with prolonged DAPT. The landmark analyses between 3 months and 3 years and per-protocol analyses showed consistent results. Conclusions and Relevance: Among patients who underwent PCI and completed 3-month DAPT, P2Y12 inhibitor monotherapy was associated with a lower risk of clinically relevant major bleeding than prolonged DAPT. Although the 3-year risk of ischemic cardiovascular events was comparable between the 2 groups, this result should be interpreted with caution owing to the limited number of events and sample size. Trial Registration: ClinicalTrials.gov Identifier: NCT02079194.
Importance: Although P2Y12 inhibitor monotherapy after a minimum period of dual antiplatelet therapy (DAPT) is a well-known way to reduce the risk of bleeding after percutaneous coronary intervention (PCI), data comparing long-term clinical outcomes between P2Y12 inhibitor monotherapy and extended DAPT in patients undergoing PCI have been unavailable. Objective: To identify the long-term safety and efficacy of P2Y12 inhibitor monotherapy following 3 months of DAPT after PCI. Design, Setting, and Participants: The Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy and Dual Antiplatelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents (SMART-CHOICE) trial was an open-label, noninferiority, randomized clinical trial, enrolling patients who underwent PCI with drug-eluting stent at 33 hospitals in Korea from March 2014 through July 2017. Clinical follow-up was extended to 3 years and completed in August 2020. Interventions: Patients were randomly assigned to either P2Y12 inhibitor monotherapy after 3 months of DAPT or DAPT for 12 months or longer. Main Outcomes and Measures: The primary end point was major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) at 3 years. The secondary end points included the components of the primary end point, bleeding (defined as Bleeding Academic Research Consortium [BARC] types 2-5), and major bleeding (BARC types 3-5). Results: In total, 2993 patients were randomly assigned to receive P2Y12 inhibitor monotherapy after 3 months of DAPT (1495 patients [50%]; mean [SD] age, 64.6 [10.7] years; 1087 [72.7%] male) or prolonged DAPT (1498 patients [50%]; mean [SD] age, 64.6 [10.7] years; 1111 [74.2%] male) after PCI. At 3 years, the primary end point occurred in 87 individuals (6.3%) in the P2Y12 inhibitor monotherapy group and 83 (6.1%) in the prolonged DAPT group (hazard ratio [HR], 1.06 [95% CI, 0.79-1.44]; P = .69). P2Y12 inhibitor monotherapy significantly reduced the risk of bleeding (BARC types 2-5: 112 [3.2%] vs 44 [8.2%]; HR, 0.39 [95% CI, 0.28-0.55]; P < .001) and major bleeding (BARC types 3-5; 17 [1.2%] vs 31 [2.4%]; HR, 0.56 [95% CI, 0.31-0.99]; P = .048), compared with prolonged DAPT. The landmark analyses between 3 months and 3 years and per-protocol analyses showed consistent results. Conclusions and Relevance: Among patients who underwent PCI and completed 3-month DAPT, P2Y12 inhibitor monotherapy was associated with a lower risk of clinically relevant major bleeding than prolonged DAPT. Although the 3-year risk of ischemic cardiovascular events was comparable between the 2 groups, this result should be interpreted with caution owing to the limited number of events and sample size. Trial Registration: ClinicalTrials.gov Identifier: NCT02079194.
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