One-month DAPT followed by 5-month Ticagrelor monotherapy in acute coronary syndromes with DCB - results from REC-CAGEFREE II

Published in Congress: EuroPCR 2024

Link: https://www.pcronline.com/News/PCR-Press-Releases/2024/EuroPCR-2024-One-month-DAPT-followed-by-5-month-Ticagrelor-monotherapy-in-acute-coronary-syndromes-with-DCB-results-from-REC-CAGEFREE-II

Dr. Yasin Özen

The REC-CAGEFREE II trial is a multicenter, open-label, non-inferiority, randomised trial that compares stepwise de-escalation of dual antiplatelet treatment (DAPT) with standard DAPT in patients treated with paclitaxel-coated balloons (PCB) for acute coronary syndrome (ACS). In contrast to traditional DAPT (aspirin plus ticagrelor for 12 months), eligible patients were randomly assigned to stepwise DAPT de-escalation, which involved aspirin plus ticagrelor for 1 month, followed by 5 months of ticagrelor monotherapy, and then 6 months of aspirin alone. A composite of all-cause death, stroke, myocardial infarction [MI], revascularization, and Bleeding Academic Research Consortium [BARC] category 3 or 5 bleeding at one year was the primary effectiveness outcome.
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.
Conclusions:
The groundbreaking REC-CAGEFREE II trial offers the first randomised information on antiplatelet treatment use in the setting of drug coated balloon (DCB). However, it's likely that the findings only apply to low-risk groups, primarily those who have single small artery disease and unstable angina. There are theoretical benefits to using DCB in the setting of ACS, such as the restoration of endothelial function and the avoidance of late acquired malapposition and delayed endothelialization. Testing these potential benefits in well-designed trials comparing the use of DCB vs drug eluting stent (DES) in de novo lesions in patients with ACS is necessary.
Comment:
This study's primary strength is that it offers the first randomised evidence on the antiplatelet therapy approach in DCB percutaneous coronary intervention (PCI). Using DCB may have the benefit of requiring shorter DAPT because there are no stent struts that need to be endothelialized. Present guidelines still support DAPT for 12 months in patients without high bleeding risk, although patients with ACS have a higher ischemic risk.
In ACS patients receiving DCB treatment, the current study demonstrates the benefit of ticagrelor de-escalation therapy. Still, there are a few crucial factors to take into account. Firstly, there is a paucity of evidence supporting the use of DCB for treating de novo lesions, especially in patients with ACS. There are no randomized studies that show satisfactory outcomes in this setting. Second, the majority of participants had unstable angina, with only about 40% undergoing PCI for either ST-elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI). It is consequently controversial to apply the findings to higher-risk STEMI or NSTEMI patients. Third, a very selective population was indicated by the fact that just 9% of all eligible patients were enrolled. The primary rationale for the exclusion was the utilization of a DES in a different channel. This raised questions regarding the external validity of the results as well as the viability of a PCB-only approach in patients with ACS, who frequently have multivessel illness. Fourth, only PCBs were employed in the treatment, and the majority of lesions treated (mean PCB diameter: 2.7 mm) were in tiny vessels. Again, this suggests a very specific, low-risk demographic, given the majority of patients had only one lesion addressed. Lastly, a variety of PCB types were employed, the majority of which lacked strong clinical support for their application in de novo lesions. These devices have no class effect; instead, a variety of parameters, including dosage, formulation, and release kinetics, affect their efficacy.