Lipid management remains a cornerstone of cardiovascular risk reduction, with persistent evidence-practice gaps in LDL-cholesterol target attainment. The therapeutic landscape spans statins, ezetimibe, bempedoic acid, PCSK9 monoclonal antibodies, and siRNA-based PCSK9 inhibitors, offering multiple escalation pathways.

Real-world prescribing analyses reveal significant shifts: PCSK9 inhibitor use rose from 33% to 40% of lipid-lowering prescriptions between the first halves of 2023 and 2024, while statin monotherapy declined from 42% to 30%. The phase 4 AMUNDSEN trial (n=2,166 acute MI patients) is evaluating early PCSK9 inhibitor initiation pre-percutaneous coronary intervention to assess whether acute-phase LDL reduction and anti-inflammatory plaque stabilization translate into improved 12-month cardiovascular outcomes. These data challenge conventional stepwise escalation and raise questions about optimal LDL targets, treatment sequencing, and cost-effectiveness across therapy classes.

Cardiologists, endocrinologists, and primary care physicians managing dyslipidemia will benefit from peer discussion of PCSK9 inhibitor positioning, combination therapy sequencing, early acute-phase intervention evidence, and strategies to improve LDL target attainment.

How do you sequence lipid-lowering therapies, including statins, ezetimibe, bempedoic acid, and PCSK9 inhibitors, in patients with high cardiovascular risk who have not achieved their LDL target? What evidence or clinical factors would lead you to consider earlier PCSK9 inhibitor initiation in the acute coronary syndrome setting, rather than following stepwise guideline-recommended escalation?