Extended Clopidogrel Monotherapy vs DAPT in Patients With Acute Coronary Syndromes at High Ischemic and Bleeding Risk
Authors: Li Yi , Li Jing , Wang Bin , Jing Quanmin , Zeng Yujie , Hou Aijie , Wang Zhifang , Liu Aijun , Zhang Jinliang , Zhang Yaojun , Zhang Ping , Jiang Daming , Liu Bin , Fan Jiamao , Zhang Jun , Li Li , Su Guohai , Yang Ming , Jiang Weihong , Qu Peng , Zeng Hesong , Li Lu , Qiu Miaohan , Ru Leisheng , Chen Shaoliang , Zhou Yujie , Qiao Shubin , Stone Gregg W. , Angiolillo Dominick J. , Han Yaling ,   OPT-BIRISK Investigators, Yang Ping , Wu Gang , Zheng Yang , Sui Liyou , Gong  Jianbin , Mi Jie , Chen Hong , Zhang Ruiyan , Su  Xi , Zhao  Xingsheng , Chen  Zhujun , Xu Biao , Pei  Hanjun , Li  Na , Cong Hongliang , Liu Jinghua , Shou  Xiling , Wang  Fengde , Yin  Da , Hu Xiaofeng , An  Jian , Zeng Chunyu , Guo  Jincheng , Ma  Genshan , Zhou Xinfu , Wang  Lefeng , Qin Qin , Zeng  Qiutang , Li  Shuangbin , Zheng Yi , Yuan Zuyi , Yang  Qing , Liu  Gang , Zhao Xianxian , Kong  Lingge , Li  Jifu , Li  Tianchang , Zhao Ruiping , Wang Hong , Li  Chunjian , Jiang Yanbo , Ma   Likun , Hou Ping , Zhang  Zixin , Li     Junxia , Zhong  Zhixiong , Du   Zhimin , Wang  Zhiyong , Chen Xuezhi , Jin Longzhe , Wang Changqian , Shen Chengxing , Zhao Gang , Liu Xiaohui , Li  Yongjun , Gao  Chuanyu , Cheng  Biao , Wang Jiang , Jin  Yuanzhe , Jin Qun , He Songjian , Zheng Zhaofen , Luo Yukun , Liu   Yingwu , Hu Taohong , Han Zhanying , Wu Weiheng , Wang Hua , Ma Yitong , Tao Jianhong , Shi Haiming , Sun Fucheng , Guo Yansong , Wu  Hongyi , Feng   Li , Zhu Jianhua , Shi Xubo , Li  Xiaodong 
Published: April 2024

ImportancePurinergic receptor P2Y12 (P2Y12) inhibitor monotherapy after a certain period of dual antiplatelet therapy (DAPT) may be an attractive option of maintenance antiplatelet treatment for patients undergoing percutaneous coronary intervention (PCI) who are at both high bleeding and ischemic risk (birisk).ObjectiveTo determine if extended P2Y12 inhibitor monotherapy with clopidogrel is superior to ongoing DAPT with aspirin and clopidogrel after 9 to 12 months of DAPT after PCI in birisk patients with acute coronary syndromes (ACS).Design, Setting, and ParticipantsThis was a multicenter, double-blind, placebo-controlled, randomized clinical trial including birisk patients with ACS who had completed 9 to 12 months of DAPT after drug-eluting stent implantation and were free from adverse events for at least 6 months at 101 China centers between February 2018 and December 2020. Study data were analyzed from April 2023 to May 2023.InterventionsPatients were randomized either to clopidogrel plus placebo or clopidogrel plus aspirin for an additional 9 months.Main Outcomes and MeasuresThe primary end point was Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding 9 months after randomization. The key secondary end point was major adverse cardiac and cerebral events (MACCE; the composite of all-cause death, myocardial infarction, stroke or clinically driven revascularization). The primary end point was tested for superiority, and the MACCE end point was tested for sequential noninferiority and superiority.ResultsA total of 7758 patients (mean [SD] age, 64.8 [9.0] years; 4575 male [59.0%]) were included in this study. The primary end point of BARC types 2, 3, or 5 bleeding occurred in 95 of 3873 patients (2.5%) assigned to clopidogrel plus placebo and 127 of 3885 patients (3.3%) assigned to clopidogrel plus aspirin (hazard ratio [HR], 0.75; 95% CI, 0.57-0.97; difference, −0.8%; 95% CI, −1.6% to −0.1%; P = .03). The incidence of MACCE was 2.6% (101 of 3873 patients) in the clopidogrel plus placebo group and 3.5% (136 of 3885 patients) in the clopidogrel plus aspirin group (HR, 0.74; 95% CI, 0.57-0.96; difference, −0.9%; 95% CI, −1.7% to −0.1%; P &amp;lt; .001 for noninferiority; P = .02 for superiority).Conclusions and RelevanceAmong birisk patients with ACS who completed 9 to 12 months of DAPT after drug-eluting stent implantation and were free from adverse events for at least 6 months before randomization, an extended 9-month clopidogrel monotherapy regimen was superior to continuing DAPT with clopidogrel in reducing clinically relevant bleeding without increasing ischemic events.Trial RegistrationClinicalTrials.gov Identifier: NCT03431142