Single vs. dual antiplatelet therapy in elderly or HBR patients undergoing percutaneous interventions with drug-coated balloons: design and rationale of PICCOLETO IV-EPIC 38 study

RATIONALE Elderly patients with obstructive coronary artery disease (CAD) frequently present a high bleeding risk (HBR). In this category of patients, percutaneous coronary intervention (PCI) is also associated with a higher risk of periprocedural and long-term ischemic and bleeding complications. PCI with drug-coated balloons (DCB) with short dual antiplatelet therapy (DAPT) is a valid alternative to stenting in this group of elderly or HBR patients. To date, no dedicated trial has prospectively evaluated the safety and efficacy of a PCI with solo-DCB followed by single antiplatelet therapy (SAPT). OBJECTIVES The study aims to evaluate the incidence of ischemic and bleeding adverse events following SAPT after only-DCB PCI in elderly patients or those with high bleeding risk, either with chronic or acute coronary syndromes. DESIGN PICCOLETO IV-EPIC38 study (clinicaltrial.gov: NCT06535568) is a prospective, international, multicenter, investigator-driven, open-label, randomized (1:1), superiority clinical trial. The study will enroll elderly patients aged 75 years or older (≥75 years) or HBR patients, as defined by the Academic Research Consortium criteria, who are undergoing successful DCB-only PCI for native coronary artery disease in vessels with a diameter between 2.0 and 4.0 mm. Participants will be randomized in a 1:1 ratio between two treatment groups: the experimental arm receiving SAPT and the comparative arm receiving DAPT. Patients in the experimental arm will receive either aspirin or clopidogrel. In the comparative arm, patients will receive standard care. The primary endpoint of this study is the incidence of Net Adverse Clinical Events (NACE), defined as the composite of major adverse cardiac events (MACE), including total mortality, target vessel revascularization, and spontaneous myocardial infarction, and clinically relevant bleeding events (BARC 2, 3, or 5), assessed over 12 months. A superiority hypothesis will be tested. A total of 576 patients will be enrolled in the study, with primary analysis conducted on an intention-to-treat basis and secondary analysis performed on an as-treated basis. Randomization will take place after successful intervention. SUMMARY The PICCOLETO IV-EPIC38 study is a randomized trial assessing the safety and efficacy of SAPT post-PCI with DCB treatment, which could significantly impact treatment for elderly or HBR patients with CAD.