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

Dear Editor

Gao et al. 2025 investigate the efficacy and safety of a stepwise de-escalation strategy for dual antiplatelet therapy (DAPT) following drug-coated balloon (DCB) angioplasty. This study addresses a pertinent clinical query regarding the optimization of antiplatelet therapy pot-DCB angioplasty [1]. Finding the equilibrium of thrombotic risk reduction and minimizing bleeding remains a key principle of Evidence-based practice (EBP). Moreover, the multicenter, randomised, assessor-blind approach enhances the study's generalizability.

However, the following areas are critical considerations. First and foremost, the open-label methodology facilitated participants’ awareness of their treatment which inherently influences their adherence and overall engagement [2]. Also, clinician knowledge often affects treatment decisions and the intensity of monitoring. The bias highlighted here can affect the internal validity of the study outcomes.

Additionally, the duration of follow-up remains a significant limitation. There is a high chance of cardiovascular effects occurring beyond the period covered by the research. Moreover, late stent thrombosis and recurrent ischemic events often manifest months or years after the intervention [3]. Thus, longer follow-up would be necessary to determine the proper risk-benefit balance of the stepwise de-escalation stratagem. Lastly, the absence of a standardised DAPT de-escalation protocol across different regions provides leeway to introducing variability in adherence and implementation [4]. Such variations often compromise the external validity of the study.

References
[1] Gao C, Zhu B, Ouyang F, Wen S, Xu Y, Jia W, et al. 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. BMJ. 2025 Mar 31;e082945.
[2] Lord-Bessen J, Signorovitch J, Yang M, Georgieva MV, Roydhouse J. Assessing the impact of open-label designs in patient-reported outcomes: investigation in oncology clinical trials. JNCI cancer spectrum [Internet]. 2023 Jan 20;7(2). Available from: https://academic.oup.com/jncics/article/7/2/pkad002/6994189
[3] Matteau A, Yeh RW, Camenzind E, Steg PG, Wijns W, Mills J, et al. Balancing Long-Term Risks of Ischemic and Bleeding Complications After Percutaneous Coronary Intervention With Drug-Eluting Stents. The American Journal of Cardiology [Internet]. 2015 Jun 6 [cited 2025 Apr 2];116(5):686–93. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC4670082/
[4] Kereiakes DJ, Yeh RW. DES and DAPT in Evolution. КАРДИОЛОГИЯ УЗБЕКИСТАНА. 2022 Feb 1;15(3):278–81.