Clinical Review of Lipid Management Strategies

How should clinicians approach patients who remain at high risk despite maximally tolerated statins?

In the post-statin era, clinicians should look beyond LDL-C alone and evaluate markers of residual risk, such as Lipoprotein(a) (Lp(a)), Apolipoprotein B (ApoB), and inflammatory markers (C-Reactive Protein). If a patient remains above risk-based thresholds, the evidence supports a “lower is better” approach by sequentially adding non-statin therapies. Ezetimibe is typically the first-line add-on due to cost and safety, followed by PCSK9 inhibitors or bempedoic acid for those requiring more intensive reduction. This strategy shifts the focus from “statin-only” to “pathway-comprehensive” risk management.

What role does bempedoic acid play in current lipid-lowering protocols?

Bempedoic acid offers a valuable alternative for patients with statin-associated muscle symptoms (SAMS) because it is a prodrug activated only in the liver, avoiding the systemic muscle effects often seen with statins. It can be used alone or in combination with ezetimibe. Clinicians should interpret its use as a tool for achieving threshold goals in primary and secondary prevention, though they must remain mindful of specific side effects like increased uric acid levels, which may predispose certain patients to gout.

Is it time to shift from LDL-C targets to more comprehensive lipid markers?

While LDL-C remains the primary target in most global guidelines, this paper suggests that for high-risk individuals—particularly those with metabolic syndrome or high triglycerides—markers like non-HDL-C and ApoB provide a more accurate assessment of the total burden of atherogenic particles. Using these markers can help clinicians identify patients who appear “controlled” on a standard lipid panel but still harbor significant vascular risk, allowing for more aggressive intervention before a clinical event occurs.