Paris, France, 14-17 May 2024. The Course Directors have selected 3 major Late Breaking Trials (LBTs) that will be presented for the first time during the 2024 edition of EuroPCR. These trials were selected on account of their design, outcomes and potential to influence daily clinical practice. Among them is the REC-CAGEFREE II trial.
Background and methods
The REC-CAGEFREE II trial is an open-label, investigator-initiated, non-inferiority, multicentre randomised trial comparing stepwise de-escalation of dual antiplatelet therapy (DAPT) with standard DAPT in patients with acute coronary syndrome (ACS) treated with paclitaxel-coated balloons (PCB). Eligible patients were randomly assigned to stepwise DAPT de-escalation − consisting of aspirin plus ticagrelor for 1 month, followed by 5 months of ticagrelor monotherapy, and then 6 months of aspirin monotherapy − compared to standard DAPT (aspirin plus ticagrelor for 12 months). The primary efficacy endpoint was net adverse clinical events (a composite of all-cause death, stroke, myocardial infarction [MI], revascularisation, and Bleeding Academic Research Consortium [BARC] type 3 or 5 bleeding) at 1 year.
Results
A total of 1,948 patients were enrolled and randomised to stepwise DAPT de-escalation (n=975) or standard DAPT (n=973). The study shows that stepwise DAPT de-escalation was non-inferior to standard 12-month DAPT for the primary endpoint in patients with ACS treated exclusively with PCB (87 [9.0%] vs 84 [8.7%]; difference: 0.3%, upper boundary of the one-sided 95% confidence interval [CI]: 2.4%; p non-inferiority=0.01). The rates of BARC type 3 or 5 bleeding were 0.4% and 1.7% (difference: −1.24%, 95 % CI: −2.14 to −0.33), and the rates of the composite of all-cause death, stroke, MI, and revascularisation were 8.8% and 7.6% (difference: 1.03%, 95 CI%: −1.40 to 3.47) in the stepwise de-escalation and standard groups, respectively.
Key learnings
The major strength of this study is that it provides the first randomised evidence regarding antiplatelet therapy strategy in drug-coated balloon (DCB) percutaneous coronary intervention (PCI). One of the potential advantages of using DCB is the need for shorter duration DAPT, given the lack of stent struts requiring endothelialisation. However, patients with ACS have higher ischaemic risk, and current guidelines still recommend DAPT for 12 months in patients without high bleeding risk.
The present study supports the value of de-escalation therapy with ticagrelor in ACS patients treated with DCB. However, some important considerations remain. First, evidence for the use of DCB in the context of de novo lesions (particularly in patients with ACS) is quite limited, with no randomised data to demonstrate adequate results in this context. Second, only around 40% of subjects underwent PCI for ST-elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI), while the rest had unstable angina. Application of the results to higher-risk patients with STEMI or NSTEMI is therefore debatable. Third, only 9% of all eligible patients were enrolled, indicating a very selected population. The main reason for exclusion was use of a drug-eluting stent (DES) in another vessel, raising concerns about the feasibility of a PCB-only strategy in patients with ACS, who often have multivessel disease, and the external validity of the data. Fourth, with regard to the procedure, only PCB were used, and 60% of the lesions treated were in small vessels (mean PCB diameter: 2.7 mm). In most patients, only one lesion was treated, again suggesting a very selected, low-risk population. Finally, several types of PCB were used, mostly without robust clinical evidence for their use in de novo lesions. There is no class effect for these devices, whose efficacy is influenced by multiple factors such as dose, formulation and release kinetics.
Conclusions and PCR recommendations
REC-CAGEFREE II is a pioneering study that provides the first randomised data concerning the use of antiplatelet therapy in the context of DCB. The results, however, are probably only applicable to low-risk populations (mainly those with unstable angina with single small vessel disease). Using DCB in the context of ACS poses theoretical advantages, including recovery of endothelial function and the lack of delayed endothelialisation and late acquired malapposition. These potential benefits require testing in adequately designed trials comparing the use of DCB in de novo lesions in ACS patients to DES (the current standard of care).
