Gao Chao, Zhu Bin, Ouyang Fan, Wen Shangyu, Xu Yanmin, Jia Wenxia, Yang Ping, He Yuquan, Zhong Yiming, Zhou Yimeng, Guo Zhifu, Shen Guidong, Ma Likun, Xu Liang, Xue Yuzeng, Hu Tao, Wang Qiong, Liu Yi, Zhang Ruining, Liu Jianzheng, Jiang Zhiwei, Xia Jielai, Garg Scot, van Geuns Robert-Jan, Capodanno Davide, Onuma Yoshinobu, Wang Duolao, Serruys Patrick, Tao Ling
Department of Cardiology, Xijing Hospital, Xi'an, China.
Department of Cardiology, Zhuzhou Central Hospital, Zhuzhou, China.
BMJ. 2025 Mar 31;388:e082945. doi: 10.1136/bmj-2024-082945.
To investigate whether a less intense antiplatelet regimen could be used for people receiving drug coated balloons.
Multicentre, randomised, open label, assessor blind, non-inferiority trial (REC-CAGEFREE II).
41 hospitals in China between 27 November 2021 and 21 January 2023.
1948 adults (18-80 years) with acute coronary syndrome who received treatment exclusively with paclitaxel-coated balloons according to the international drug coated balloon consensus.
Participants were randomly assigned (1:1) to either the stepwise dual antiplatelet therapy (DAPT) de-escalation group (n=975) consisting of aspirin plus ticagrelor for one month, followed by five months of ticagrelor monotherapy, and then six months of aspirin monotherapy, or to the standard DAPT group (n=973) consisting of aspirin plus ticagrelor for 12 months.
The primary endpoint was net adverse clinical events (all cause death, stroke, myocardial infarction, revascularisation, and Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding) at 12 months in the intention-to-treat population. Non-inferiority was established if the upper limit of the one sided 95% confidence interval (CI) for the absolute risk difference was smaller than 3.2%.
The mean age of participants was 59.2 years, 74.9% were men, 30.5% had diabetes, and 20.6% were at high bleeding risk. 60.9% of treated lesions were in small vessels, and 17.8% were in-stent restenosis. The mean drug coated balloon diameter was 2.72 mm (standard deviation 0.49). At 12 months, the primary endpoint occurred in 87 (8.9%) participants in the stepwise de-escalation group and 84 (8.6%) in the standard group (difference 0.36%; upper boundary of the one sided 95% CI 2.47%; P=0.013). In the stepwise de-escalation versus standard groups, BARC type 3 or 5 bleeding occurred in four versus 16 participants (0.4% 1.6%, difference -1.19% (95% CI -2.07% to -0.31%), P=0.008), and all cause death, stroke, myocardial infarction, and revascularisation occurred in 84 versus 74 participants (8.6% 7.6%, difference 1.05% (95% CI -1.37% to 3.47%), P=0.396). Treated as having hierarchical clinical importance by the win ratio method, more wins were noted with the stepwise de-escalation group (14.4% wins) compared with the standard group (10.1% wins) for the predefined hierarchical composite endpoint of all cause death, stroke, myocardial infarction, BARC type 3 bleeding, revascularisation, and BARC type 2 bleeding (win ratio 1.43 (95% CI 1.12 to 1.83), P=0.004). Results from the per-protocol and the intention-to-treat analysis were similar.
Among participants with acute coronary syndrome who could be treated by drug coated balloons exclusively, a stepwise DAPT de-escalation was non-inferior to 12 month DAPT for net adverse clinical events.
Clinicaltrials.gov NCT04971356.
探讨对于接受药物涂层球囊治疗的患者，是否可采用强度较低的抗血小板治疗方案。
多中心、随机、开放标签、评估者盲法、非劣效性试验（REC-CAGEFREE II）。
2021年11月27日至2023年1月21日期间中国的41家医院。
1948名年龄在18 - 80岁之间的急性冠脉综合征成人患者，根据国际药物涂层球囊共识，这些患者仅接受紫杉醇涂层球囊治疗。
参与者被随机分配（1:1）至逐步双联抗血小板治疗（DAPT）降阶梯组（n = 975），该组先给予阿司匹林加替格瑞洛治疗1个月，随后5个月单药使用替格瑞洛，然后6个月单药使用阿司匹林；或标准DAPT组（n = 973），给予阿司匹林加替格瑞洛治疗12个月。
主要终点为意向性治疗人群在12个月时的净不良临床事件（全因死亡、卒中、心肌梗死、血运重建以及出血学术研究联盟（BARC）3型或5型出血）。如果绝对风险差异的单侧95%置信区间（CI）上限小于3.2%，则判定为非劣效。
参与者的平均年龄为59.2岁，74.9%为男性，30.5%患有糖尿病，20.6%为高出血风险患者。60.9%的治疗病变位于小血管，17.8%为支架内再狭窄。药物涂层球囊的平均直径为2.72 mm（标准差0.49）。在12个月时，逐步降阶梯组87名（8.9%）参与者和标准组84名（8.6%）参与者发生了主要终点事件（差异0.36%；单侧95%CI上限2.47%；P = 0.013）。在逐步降阶梯组与标准组中，BARC 3型或5型出血分别发生在4名和16名参与者中（0.4%对1.6%，差异 -1.19%（95%CI -2.07%至 -0.31%），P = 0.008），全因死亡、卒中、心肌梗死和血运重建分别发生在84名和74名参与者中（8.6%对7.6%，差异1.05%（95%CI -1.37%至3.47%），P = 0.396）。采用获胜比方法将其视为具有分层临床重要性，对于全因死亡、卒中、心肌梗死、BARC 3型出血、血运重建和BARC 2型出血的预定义分层复合终点，逐步降阶梯组的获胜次数更多（获胜率14.4%），高于标准组（获胜率10.1%）（获胜比1.43（95%CI 1.12至1.83），P = 0.004）。符合方案分析和意向性治疗分析的结果相似。
在仅可接受药物涂层球囊治疗的急性冠脉综合征参与者中，逐步DAPT降阶梯在净不良临床事件方面不劣于12个月的DAPT。
Clinicaltrials.gov NCT04971356。
