Association between P2Y12 inhibitor reloading and in-hospital outcomes for patients with non-ST-segment elevation acute coronary syndrome already on chronic P2Y12 receptor inhibitors therapy in China: findings from the CCC–ACS (improving care for cardiovascular disease in China-acute coronary syndrome) project
Authors: Wang Yintang , Geng Yu , Zhang Ou , Xu Qin , Xue Yajun , Zhou Boda , Zhang Ping ,   the CCC-ACS Investigators, Li Aihua , Li Bao , Xu Biao , Han Guangshu , Li Bin , Liu Bin , Wang Bin , Fu Bing , Yu Bo , Yang Bosong , Luo Caidong , Wang Changqian , Liu Changyong , Liang Chuanliang , Gao Chuanyu , Lai Chunlin , Wang Chuntong , Zhang Chunyan , Wu Chunyang , Zhang Congliang , Bin Cui , Huang Lan , Peng Daoquan , Xu Dawen , Wu Di , Zhu Dongmei , Chai Dongsheng , Li Dongyan , Tang Fakuan , Xiao Jun , Zhao Fang , Huang Fangfang , Meng Fanju , Li Fengwei , Gan Fudong , Xu Gang , Sang Gengsheng , Ma Genshan , Zhang Guixia , Tao Guizhou , Li Guo , Chen Guoduo , Xin Guoqin , Li Guoqing , Fu Guosheng , Chen Guoxiong , Lin Hailong , Guo Haiping , Lin Haiyun , Jiang Hong , Liu Hong , Luan Hong , Zhang Hong , Deng Honghua , Li Hongwei , Wang Honhju , Liu Hualing , Dong Hui , Liu Hui , Zhang Huifang , Wang Huifeng , Chu Huimin , Xi Jiabin , Yang Jian , Ye Jianfeng , Li Jianhao , Tao Jianhong , Liu Jianwen , Yang JiaoMei , Ding Jiawang , Tong Jiayi , Chen Jie , Jiang Jie , Yang Jie , Li Jifu , Yan Jinchuan , Hu Jing , Xu Jing , Wang Jingfeng , Diao Jinglan , Zhao Jingshan , Wei Jinru , Yi Jinxing , Su Jinzi , Tang Jiong , Chen Jiyan , Yin Jiyan , Fan Juexin , Guan Jun , Ge Junbo , Liu Junming , Deng Junping , Fang Junping , Li Junxia , Chen Kaihong , Luo Kalan , Wu Keng , Ji Lang , Li Lang , Jiang Li , Wei Li , Meng Lijun , Ma Likun , Tang Lilong , Wang Lin , Wei Lin , Li Ling , Tao Ling , Yang Liqiong , Wu Lirong , Zhang Man , Chen Kaiming , Lai Meisheng , Tian Miao , Bai Mingcheng , Han Minghua , Chen Moshui , Liang Naiyi , Jia Nan , Zhang Peiying , Qu Peng , Zhang Pengfei , Chen Ping , Hou Ping , Xie Ping , Dong Pingshuan , Wu Qiang , Xie Qiang , Zhong Qiaoqing , Wang Qichun , Su Qinfeng , Chang Rong , Lin Rong , Zhao Ruiping , Jia Shaobin , Nie Shaoping , Ye Shaowu , He Shenghu , Chen Shengyong , Ma Shixin , Li Shuangbin , Xin Shuanli , Xia Shudong , Zhang Shuhua , Qu Shuqiu , Ma Shuren , Wang Siding , Li Songbai , Luo Suxin , Liu Tao , Zhang Tao , Tuo Tian , Li Tianchang , Yang Tianlun , Du Tianmin , Wu Tongguo , Liu Wei , Mao Wei , Tuo Wei , Wang Wei , Jiang Weihong , Huang Weijian , Liu Weijun , Fan Weiqing , Xu Weiting , Lin Wenhua , Su Xi , Chen Xia , Zhang Xianan , Fu Xianghua , Yang Xiangjun , Zhao Xianxian , Ma Xiaochuan , Sun Xiaofei , Wang Xiaojun , Li Xiaolan , Li Xiaolei , Yang Xiaoli , Chen Xiaoping , Zhang Xiaoqin , Cheng Xiaoshu , Peng Xiaowei , Ma Xiaowen , Qi Xiaoyong , Feng Xiaoyun , Chen Ximing , Tang Xin , Tang Xingsheng , Zhao Xingsheng , Chen Xiufeng , Li Xudong , Li Xue , Liu Xuebo , Peng Xuemei , Han Yaling , Wang Yan , Niu Yanbo , Yu Yang , Zheng Yang , Wang Yanli , Zheng Yanlie , Guo Yansong , Yang Yanzong , Huang Yi , Liu Yin , Guo Ying , Luo Yingchao , Hao Yinglu , Sun Yingxian , Lin Yingzhong , Ma Yitong , Guo Yong , Li Yong , Li Yongdong , Zhang Yonglin , Jin Yuanzhe , Li Yue , Huang Yuehua , Sun Yuemin , Yang Yuheng , Zhu Yuhua , Shi Yuhuan , Zhao Yulan , Hou Yuqing , Zheng Zeqi , Xu Zesheng , Ouyang Zewei , He Zeyuan , Lv Zhan , Li Zhanquan , He Zhaofa , Ji Zheng , Zhang Zheng , Ji Zhenguo , Su Zhenqi , Yang Zhenyu , Ou Zhihong , Yang Zhijian , Yang Zhiming , Wang Zhirong , Song Zhiyuan , Wang Zhongshan , Yuan Zuyi 
Published: February 2023

Abstract
Background
The association between P2Y12 receptor inhibitors reloading and in-hospital outcomes in non-ST-segment elevation acute coronary syndrome (NSTEACS) patients who were on chronic P2Y12 receptor inhibitors therapy remained underdetermined.

Methods
The Improving Care for Cardiovascular Disease in China–Acute Coronary Syndrome (CCC–ACS project) is a national registry active from November 2014 to December 2019. 4790 NSTEACS patients on chronic P2Y12 receptor inhibitors therapy were included. Cox proportional hazard models, Kaplan–Meier curves, and subgroup analyses were conducted.

Results
The NSTEACS patients who received reloading of P2Y12 receptor inhibitors were younger and had fewer comorbid conditions. The reloading group had a lower risk of major adverse cardiac events (MACE) (0.51% vs. 1.43%, P = 0.007), and all-cause death (0.36% vs. 0.99%, P = 0.028), the risks of myocardial infarction and major bleeding were not significantly different between patients with and without reloading. In survival analysis, a lower cumulative risk of MACE could be identified (Log-rank test, P = 0.007) in reloading group. In the unadjusted Cox model, reloading P2Y12 receptor inhibitors was associated with a decreased risk of MACE [HR, 0.35; 95% CI 0.16–0.78; (P = 0.010)] and all-cause death [HR, 0.37; 95% CI 0.14–0.94; (P = 0.036)]. Reloading of P2Y12 receptor inhibitors was associated with a decreased risk of MACE in most of the subgroups.

Conclusions
In NSTEACS patients already taking P2Y12 receptor inhibitors, we observed a decreased risk of in-hospital MACEs and all-cause mortality and did not observe an increased risk of major bleeding, with reloading. The differential profile in the two groups might influence this association and further studies are warranted.
Clinical trial registration: https://www.clinicaltrials.gov (Unique identifier: NCT02306616, date of first registration: 03/12/2014)