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
Authors: Chao Gao, Bin Zhu, Fan Ouyang, Shangyu Wen, Yanmin Xu, Wenxia Jia, Ping Yang, Yuquan He, Yiming Zhong, Yimeng Zhou, Zhifu Guo, Guidong Shen, Likun Ma, Liang Xu, Yuzeng Xue, Tao Hu, Qiong Wang, Yi Liu, Ruining Zhang, Jianzheng Liu, Zhiwei Jiang, Jielai Xia, Scot Garg, Robert-Jan van Geuns, Davide Capodanno, Yoshinobu Onuma, Duolao Wang, Patrick Serruys, Ling Tao
Journal: BMJ (2025)

Abstract Objectives To investigate whether a less intense antiplatelet regimen could be used for people receiving drug coated balloons. Design Multicentre, randomised, open label, assessor blind, non-inferiority trial (REC-CAGEFREE II). Setting 41 hospitals in China between 27 November 2021 and 21 January 2023. Participants 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. Interventions 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. Main outcome measures 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%. 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. 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 non-inferiority =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). 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. 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. Trial registration Clinicaltrials.gov NCT04971356