Stepwise dual antiplatelet therapy de-escalation versus standard therapy for 12 months in patients with bifurcation lesions undergoing drug-coated balloon angioplasty: Insights from the REC-CAGEFREE II trial

Background: The optimal antiplatelet strategy for patients with acute coronary syndrome (ACS) and bifurcation lesions undergoing drug-coated balloon (DCB) angioplasty remains unclear. Methods: This was a prespecified subgroup analysis of the REC-CAGEFREE II trial, which randomized 1948 ACS patients undergoing DCB-only angioplasty to stepwise dual antiplatelet therapy (DAPT) de-escalation (1-month aspirin plus ticagrelor, 5-month ticagrelor monotherapy, 6-month aspirin monotherapy) or standard DAPT (12-month aspirin plus ticagrelor). Participants were stratified into bifurcation and non-bifurcation subgroups based on whether any target lesion involved a bifurcation, with inverse probability of treatment weighting (IPTW) applied to adjust for imbalances. The primary endpoint was 12-month net adverse clinical events (NACE), defined as a composite of the patient-oriented composite endpoint (PoCE: all-cause death, stroke, myocardial infarction, or revascularization) and Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. Results: Among 1948 patients, 884 (45.4%) were in the bifurcation subgroup. At 12 months, no significant interaction was observed between bifurcation/non-bifurcation and treatment strategy for NACE (Pinteraction = 0.221). In the bifurcation subgroup, NACE occurred in 51/447 (11.5%) patients receiving stepwise DAPT de-escalation and in 41/437 (9.4%) patients receiving standard DAPT (HRIPTW:1.15, 95%CI:0.75–1.77, P = 0.509). PoCE did not differ significantly between stepwise DAPT de-escalation and standard DAPT groups (11.0% versus 8.0%, HRIPTW:1.39, 95%CI:0.89–2.16, P = 0.153), whereas stepwise DAPT de-escalation was associated with a lower incidence of BARC type 3 or 5 bleeding (0.5% versus 1.8%, HRIPTW,0.15, 95%CI:0.03–0.72, P = 0.048). Conclusions: Stepwise DAPT de-escalation may be a safe and effective strategy for ACS patients with bifurcation lesions undergoing DCB-only angioplasty.