Weekly Journal Scan: VESALIUS-CV extends PCSK9 inhibition to the prevention of first major cardiovascular events

This comment refers to ‘Evolocumab in Patients without a Previous Myocardial Infarction or Stroke’ published in the New England Journal of Medicine; https://doi.org/10.1056/NEJMoa2514428. Low-density lipoprotein cholesterol has been recognized as a central and modifiable determinant of ASCVD across the whole cardiovascular disease continuum. In individuals with silent atherosclerosis or high-risk metabolic conditions such as diabetes, or in patients with prior MI or stroke, lowering LDL-C by 1 mmol/L (∼39 mg/dL) consistently yields a 20%–25% reduction in major vascular events. This relationship has been demonstrated consistently across statin, ezetimibe, and PCSK9-inhibitor clinical trials,2–4 supported by Mendelian randomization studies,5,6 and confirmed by large meta-regression analyses of the Cholesterol Treatment Trialists’ Collaboration (CTTC).7,8 These converging lines of evidence have driven the progressive shift in clinical guidelines toward lower LDL-C targets, under the premise that each incremental LDL-C reduction confers proportional clinical benefits.9,10 Nonetheless, robust outcome data for non-statin LDL-C lowering in the primary prevention of cardiovascular events among high-risk individuals are not available.