This international, multicenter, open-label, randomized clinical trial evaluates the safety and efficacy of single antiplatelet therapy (SAPT) compared to dual antiplatelet therapy (DAPT) in elderly or high bleeding risk patients undergoing percutaneous coronary intervention (PCI) with the latest generation drug-coated balloon (DCB). The study includes patients with stable or unstable coronary syndromes and aims to assess rates of ischemic and bleeding adverse events.

The purpose of the PICCOLETO IV-EPIC 38 study is to observe and evaluate the efficacy and safety of single antiplatelet therapy (SAPT) after successful PCI with the Essential Pro drug-coated balloon in native coronary artery disease in vessels with a diameter between 2.0 and 4.0 mm, compared to routine dual antiplatelet therapy (DAPT). Patients aged 75 years or older, or those at high bleeding risk, with stable or unstable coronary syndromes will be enrolled and randomized in this study.

Inclusion Criteria:

Male and female patients who meet the following criteria:

• Age ≥ 75 years or age ≥ 18 years at high bleeding risk;
• Successful PCI with Essential Pro DCB just performed, in 1, 2 or 3 coronary vessels;
• Stable or unstable coronary syndromes;
• De novo coronary lesions in vessels with diameter ≥2.0 and ≤4.0 mm (visual estimation);
• Informed consent to participate in the study given by the patient or impartial witness.

Exclusion Criteria:

• Stent implantation during index or recent (<6 months) procedure;

• Known (and untreatable) hypersensitivity or contraindication to aspirin, heparin, clopidogrel, paclitaxel or contrast media, or any of their excipient which cannot be adequately pre-medicated;

• Pregnancy at the time of hospitalization;

• Patients participating in another clinical study in which an investigational drug or device was administered within 30 days of screening or within the 5 half-lives of the study drug, whichever is longer;

• ST-elevation myocardial infarction;

• Life expectancy <12 months;

• Left ventricular ejection fraction <30%;

• Visible thrombus at lesion site;

• Target lesion/vessel with any of the following characteristics:

  • severe and/or >270° calcification of the target vessel, also proximal to the lesion (intravascular imaging not mandatory);
  • left main stem stenosis >50%;
  • target lesion is in the left main stem;
  • chronic total occlusion with anticipated necessity of retrograde approach;
  • lesion is in a bypass graft.

• History of asthma induced by the administration of salicylates or substances with a similar action, notably non-steroidal anti-inflammatory medicines (NSAIDs);

• History of gastrointestinal perforation, ulceration, or bleeding (peptic ulcer bleeding-PUBs) related to previous use of NSAIDs or anticoagulant medications, or intracranial hemorrhage;

• Acute gastrointestinal ulcers;

• Hemorrhagic diathesis (including known bleeding disorders or ongoing active bleeding);

• Severe renal impairment (eGFR < 30 mL/min);

• Severe hepatic impairment (Child-Pugh C), with elevated liver enzymes (ALT/AST > 2 x ULN or total bilirubin >1.5 x ULN);

• Severe cardiac failure (NYHA grade III or IV);

• Combination with methotrexate at doses of 15 mg/week or more;

• Patients with baseline neutrophil counts < 1500 cells/mm³;

• Breastfeeding women;

• Full-blown thyrotoxicosis;

• Patients with a very high risk of thrombosis.