The end of the primary-secondary prevention dichotomy in high-risk diabetes? Lessons from VESALIUS-CV.

The VESALIUS-CV trial was the first dedicated cardiovascular-outcomes study to demonstrate that adding the PCSK9 inhibitor evolocumab to statin therapy prevents a first major cardiovascular event in patients without a previous myocardial infarction or stroke. A prespecified analysis extended this benefit to patients with diabetes and no known significant atherosclerosis, in whom intensive low-density lipoprotein cholesterol (LDL-C) lowering reduced major adverse cardiovascular events by approximately one third. These findings challenge the long-standing reliance on the primary-secondary prevention distinction to determine the intensity of lipid-lowering therapy. We argue that in high-risk diabetes-a systemic immunometabolic syndrome characterised by adiposopathy, insulin resistance, chronic inflammation and atherogenic dyslipidaemia-the arterial wall is biologically diseased long before a first clinical event. Cardiovascular prevention in this population should therefore move from an event-based to a biology-based paradigm, governed by biological risk rather than by event history.