Stepwise dual antiplatelet therapy de-escalation in patients after drug coated balloon angioplasty (REC-CAGEFREE II): multicentre, randomised, open label, assessor blind, non-inferiority trial.

Methods

Multicentre, randomised, open label, assessor blind, non-inferiority trial (REC-CAGEFREE II).

多中心、随机、开放标签、评估者盲法、非劣效性试验（REC-CAGEFREE II）。

41 hospitals in China between 27 November 2021 and 21 January 2023.

2021年11月27日至2023年1月21日期间，中国41家医院参与。

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.

1948名年龄在18至80岁之间的急性冠状动脉综合征成人患者，仅使用紫杉醇涂层球囊进行治疗，符合国际药物涂层球囊共识。

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.

参与者被随机分配（1:1）到逐步双抗血小板治疗（DAPT）降级组（n=975），包括阿司匹林加替格瑞洛治疗一个月，随后五个月的替格瑞洛单药治疗，然后六个月的阿司匹林单药治疗，或标准DAPT组（n=973），包括阿司匹林加替格瑞洛治疗12个月。

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-treatpopulation.

主要终点是在意向治疗人群中12个月时的净不良临床事件（全因死亡、中风、心肌梗死、再血管化和出血学术研究联合会（BARC）3型或5型出血）的复合终点。

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%.

如果单侧95%置信区间（CI）的绝对风险差异上限小于3.2%，则确定非劣效性。

Results

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.

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%处于高出血风险。治疗的病变中有60.9%位于小血管，17.8%为支架内再狭窄。

The mean drug coated balloon diameter was 2.72 mm (standard deviation 0.49).

药物涂层球囊的平均直径为2.72毫米（标准差为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%; Pnon-inferiority=0.013).

在12个月时，主要终点事件在逐步降阶组的87名（8.9%）参与者和标准组的84名（8.6%）参与者中发生（差异为0.36%；单侧95%置信区间的上限为2.47%；非劣效性P值=0.013）。

In the stepwise de-escalation versus standard groups, BARC type 3 or 5 bleeding occurred in four versus 16 participants (0.4% v 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% v 7.6%, difference 1.05% (95% CI -1.37% to 3.47%), P=0.396).

在逐步降级与标准治疗组中，BARC 3型或5型出血发生在四名与十六名参与者中（0.4%对比1.6%，差异-1.19%（95%置信区间-2.07%至-0.31%），P=0.008），全因死亡、中风、心肌梗死和血运重建发生在84名与74名参与者中（8.6%对比7.6%，差异1.05%（95%置信区间-1.37%至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).

通过胜率方法评估具有层次重要性的临床结果，对于预定义的层次复合终点（全因死亡、中风、心肌梗死、BARC 3型出血、血运重建和BARC 2型出血），逐步降级组的胜率（14.4%）高于标准组（10.1%）（胜率1.43（95%置信区间1.12至1.83），P=0.004）。

Results from the per-protocol and the intention-to-treatanalysis were similar.

按方案分析和意向治疗分析的结果相似。

Conclusions

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.

在那些仅能通过药物涂层球囊治疗的急性冠状动脉综合征患者中，逐步降级的双联抗血小板治疗对于净不良临床事件并不劣于12个月的双联抗血小板治疗。

trial_registration

Clinicaltrials.gov NCT04971356.

临床试验注册编号 NCT04971356。