New Dyslipidaemia Guide Reveals Why Most High-Risk Patients Miss LDL Targets

Atherosclerotic cardiovascular disease (ASCVD) is the world's leading cause of death, with dyslipidaemia—particularly elevated LDL-C—as a central, modifiable causal driver. Yet despite the availability of highly effective lipid-lowering drugs, the condition remains chronically undertreated. In Germany, national survey data show dyslipidaemia prevalence of roughly 65% in both sexes, with more than half of cases previously undiagnosed. Real-world data from the 2022–2023 Lipid-Snapshot-Study paint a stark picture: only 27% of ASCVD patients under cardiologist care and approximately 12% under GP care reached the guideline-recommended LDL-C target of less than 55 mg/dL, while 26% of GP-managed patients received no lipid-lowering therapy at all.

This comprehensive review, authored by a multidisciplinary team of German and European cardiologists, consolidates practical guidance on lipid diagnostics, risk stratification, and evidence-based therapy. Beyond LDL-C, the authors emphasize the clinical importance of ApoB—a direct measure of all atherogenic lipoprotein particles and a stronger predictor of cardiovascular events than LDL-C in conditions such as metabolic syndrome, obesity, and diabetes. Lipoprotein(a) [Lp(a)], which is primarily genetically determined, is highlighted as a critical residual risk factor with pro-atherogenic, pro-inflammatory, and pro-thrombotic properties, warranting at least one measurement in every patient. Remnant cholesterol and triglycerides also contribute to residual ASCVD risk beyond LDL-C control.

The review integrates the 2025 ESC/EAS Focused Update to the 2019 dyslipidaemia guidelines. While LDL-C targets remain unchanged (less than 55 mg/dL for very-high-risk patients, less than 70 mg/dL for high-risk), two major new recommendations stand out. First, cardiovascular risk modifiers such as elevated Lp(a) and high-sensitivity CRP, as well as inflammatory diseases, should now formally be incorporated into risk assessment—particularly in younger adults where standard scoring tools may underestimate lifetime risk. Second, potent early combination lipid-lowering therapy is now recommended immediately following acute coronary syndrome, rather than sequential stepwise escalation, to achieve rapid and sustained LDL-C reduction.

Therapeutically, statins remain the cornerstone of treatment. Ezetimibe and bempedoic acid serve as valuable add-ons, especially for patients with statin intolerance. PCSK9 inhibitors—both monoclonal antibodies (evolocumab, alirocumab) and the small interfering RNA agent inclisiran—offer powerful LDL-C reductions of 50–60% on top of other therapies and are indicated for high- and very-high-risk patients not meeting targets. Looking ahead, RNA-based therapies targeting Lp(a) (e.g., pelacarsen, olpasiran) and novel agents affecting ANGPTL3 and PCSK9 are in advanced clinical development, promising more individualized and potentially infrequent dosing strategies.

The authors also address diagnostic nuances: the Friedewald formula for LDL-C estimation is unreliable at triglyceride levels above 400 mg/dL, and non-fasting samples are acceptable given equivalent prognostic value to fasting samples. Lp(a) assay standardization remains a challenge, with recommendations to report in mg/dL unless isoform-insensitive calibration is confirmed. The review underscores that improved awareness, systematic screening, and adherence to combination therapy protocols are urgently needed to close the persistent treatment gap.