DOI: 10.1001/jamacardio.2024.0534 ISSN: 2380-6583

Extended Clopidogrel Monotherapy vs DAPT in Patients With Acute Coronary Syndromes at High Ischemic and Bleeding Risk

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

Importance

Purinergic 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).

Objective

To 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 Participants

This 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.

Interventions

Patients were randomized either to clopidogrel plus placebo or clopidogrel plus aspirin for an additional 9 months.

Main Outcomes and Measures

The 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.

Results

A 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 < .001 for noninferiority; P = .02 for superiority).

Conclusions and Relevance

Among 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 Registration

ClinicalTrials.gov Identifier: NCT03431142

More from our Archive