Effects of Functional Bovine Milk Supplementation on Coronary In-Stent Restenosis and Major Adverse Cardiovascular Events in STEMI Patients Undergoing Primary PCI: A Randomized, Double-Blind, Controlled Trial

Coronary artery disease remains a leading cause of morbidity and mortality worldwide. Despite advances in percutaneous coronary intervention (PCI) and the use of drug-eluting stents (DES), in-stent restenosis (ISR) continues to occur, driven by neointimal hyperplasia, vascular inflammation, and metabolic dysregulation. Nutritional interventions with specific bioactive compounds may offer an innovative adjunct to secondary prevention strategies.

This investigator-initiated, randomized, double-blind, controlled trial will assess whether functionalized bovine milk (FM) - standardized to contain a defined profile of bioactive peptides with antihypertensive, anti-thrombotic, anti-inflammatory, antioxidant, and plaque-stabilizing properties - can reduce ISR incidence and improve cardiovascular outcomes in patients with a first ST-elevation myocardial infarction (STEMI) treated with PCI and DES.

A total of 140 eligible patients will be randomized 1:1 to receive FM or an isocaloric non-functional milk (NFM) for 12 months, in addition to guideline-directed secondary prevention care. Both products will be organoleptically matched, blinded by coded packaging, and supplied in equal volumes.

The primary endpoint is the proportion of patients with ISR at 12 months, as measured by coronary computed tomography angiography (CCTA). Secondary endpoints include the composite of major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for heart failure), changes in insulin secretion and sensitivity, systemic inflammatory markers (hsCRP, IL-6, TNF-α), oxidative stress parameters, serum sirtuins, and metabolomic/lipidomic profiles obtained through LC-MS and GC-MS. Myocardial injury and viability will also be quantified by cardiac positron emission tomography (PET) at baseline and at study completion.

Adherence will be monitored through dietary records, packaging return counts, and optional biochemical markers. An independent Data Safety Monitoring Board (DSMB) will oversee patient safety and trial conduct. The study is powered to detect a 50% relative reduction in ISR (from 30% to 15%) with 80% power and a two-sided alpha of 0.05.