EUROpean pragmatic multicenter randomized trial on platelet inhibition and/or lipid lowering treatment in Covert Brain Infarction

Background MRI frequently reveals covert brain infarcts — silent lacunar or cortical infarcts found incidentally. CBIs carry increased risks of stroke and death, yet guidelines offer no treatment recommendation due to lack of randomized evidence. Objective To test whether starting antiplatelet therapy (APT) and/or statins after MRI-detected CBI, in addition to risk-factor management, improves clinical outcomes. Methods EURO-CBI is an investigator-initiated, pragmatic, multicenter, phase III PROBE trial with a 2×2 factorial randomized-block design. We will randomize 1,652 participants 1:1:1:1 to control (no APT/statin), APT alone, statin alone, or APT+statin. Follow-up at 12 and 36 months is conducted by telephone with standardized assessments. A blinded Clinical Event Committee adjudicates outcomes; an independent Data Monitoring Committee oversees safety. Population Adults ≥50 years with MRI-confirmed covert lacunar and/or cortical infarct, functionally independent (mRS ≤3), and no history of symptomatic stroke/TIA. Key exclusions include high bleeding risk, dementia, progressive cancer, long-term anticoagulation, or current APT. Results Primary endpoints: Cumulative incidence of Major Adverse Cardiac and Cerebral Events (MACCE: all-cause mortality, acute myocardial infarction, stroke) through 36 months. (Efficacy) Major or fatal bleeding through 36 months. (Safety) Secondary endpoints Dementia incidence and cognitive decline; cardiovascular mortality; serious adverse events; quality of life, frailty, functional status; inflammatory and MRI biomarkers. Imaging sub-studies will quantify small-vessel-disease progression on a repeated MRI after 3 years and ultrasound-based vascular markers at baseline. In Denmark, registry-based follow-up at 5 and 10 years will assess long-term MACCE, bleeding, dementia, and mortality. Ethics/impact APT and statins are widely used after ischemic events and have well-characterized safety (bleeding with APT; mostly mild statin effects). The trial entails one on-site visit plus telephone follow-ups; medication is dispensed on-site or shipped. Given the high prevalence of CBI and lack of guidance.