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.