A paradigm shift in lipid management – „the sooner, the lower, the better“

The 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias marks a significant evolution in cardiovascular (CV) risk prevention, and it delivers nothing short of a paradigm shift. Incorporating new evidence from major trials up to March 2025, this update moves decisively towards a more personalized, aggressive, and earlier interventional approach.

Key changes include the adoption of the SCORE2/SCORE2-OP algorithms for both fatal and non-fatal event prediction, a stronger emphasis on risk modifiers for patient reclassification, and a significant expansion of treatment options, including a Class I recommendation for bempedoic acid. This update provides clinicians with evidence-based strategies to achieve lower LDL-C targets sooner (Fig. 1). In particular, it provides the practicing clinician with new strategies for managing acute coronary syndromes, specific populations like people with HIV (PWH) and oncology patients, and a definitive move away from non-evidence-based dietary supplements.

© Mach F et al. Eur Heart J 2025 00, 1–20

Fig. 1: Legend for graphical abstract: 2025 ESC/EAS Dyslipidaemia Guidelines. The 2025 ESC/EAS Guidelines mark a paradigm shift in cardiovascular risk management, championing a “sooner, lower, better” approach. These evidence-based updates provide clinicians with robust tools for personalized cardiovascular risk reduction across diverse patient populations

Refined risk estimation: the foundation of treatment

A fundamental shift is the replacement of the old SCORE algorithm with SCORE2 (ages 40–69) and SCORE2-OP (ages 70–89).¹ This is a critical advancement as it estimates the 10-year risk of both fatal and non-fatal CV events, extending sophisticated risk assessment to the elderly population. The new risk categories (low, moderate, high, very high) are based on doubled SCORE2 thresholds, reminding us that these are pragmatic cut-offs on a continuous risk spectrum.

Impactful is also the enhanced role of risk modifiers in moderate-risk patients. The presence of subclinical atherosclerosis, as detected by imaging (e.g., carotid plaque) or an elevated coronary artery calcium (CAC) score, should be considered a risk-enhancing factor that can modify risk assessment in adults estimated to be at moderate risk or in those near treatment thresholds based on the SCORE2/SCORE2-OP algorithms.¹ An important caveat is that the interpretation of a CAC score must be approached with caution in patients already on statin therapy. Statins promote plaque stabilisation, which can manifest as a decrease in lipid-rich plaque and a potential increase in calcification; therefore, a rising CAC score in this context may not indicate disease progression but rather a treatment effect (Table 1).

Table 1: Cardiovascular Risk Categories (based on SCORE2/SCORE2-OP) - updated of table 4 from the 2019 guidelines

The update also formally recognizes biomarkers, specifically elevated lipoprotein(a) [Lp(a)] >50mg/dL (105nmol/L) and high-sensitivity C-reactive protein (hs-CRP >2mg/L). These can and should be used to reclassify patients to a higher risk category, justifying more aggressive LDL-C targets and earlier intervention.¹ The new recommendation highlights that assessment should be made in the broader context of the patient’s overall risk profile, which includes the following clinical and demographic risk modifiers: family history of premature CVD (men <55 years; women <60 years), high-risk ethnicity (e.g., South Asian), socioeconomic deprivation, major psychosocial stress, or psychiatric disorders, obesity and physical inactivity, history of premature menopause, pre-eclampsia, hypertensive disorders of pregnancy, chronic inflammatory disorders (e.g., rheumatoid arthritis), HIV infection, or obstructive sleep apnoea.¹

Intensified LDL-C goals and expanded therapeutic arsenal

The LDL-C goals remain stratified by risk, but the context for setting them is now sharper. The emphasis on achieving a ≥50% reduction from baseline alongside absolute targets is reinforced across all categories, highlighting the importance of both relative intensity and absolute goal fulfilment.

The landscape of available therapeutics has expanded significantly

Based on the 2025 Focused Update, LDL-C goals remain risk-stratified, with reinforced emphasis on achieving both a ≥50% reduction from baseline and absolute targets.¹

Key therapeutic updates include a Class I recommendation for bempedoic acid in statin-intolerant patients, supported by the CLEAR Outcomes trial demonstrating 13% MACE reduction despite risks of hepatic enzyme elevation, hyperuricaemia, gout, and renal impairment (Table 2).²

Table 2: New and updated Pharmacological Treatment Recommendations from the 2025 ESC/EAS Focused Update¹

For combination therapy, non-statin agents (ezetimibe, PCSK9 mAbs, or bempedoic acid) are recommended (Class I, Level A) added to maximally tolerated statins, with selection based on required LDL-C lowering, preference, and cost (Table 2).

Evinacumab receives a Class IIa recommendation for homozygous FH patients ≥5 years, reducing LDL-C by nearly 50%¹ (Table 2).

Inclisiran remains under investigation. Clinicians should individualise therapy, monitor LDL-C 4–6 weeks post-initiation, and refer to efficacy data (Table 1).

Acute coronary syndromes: mandating in-hospital, intensive intervention

The update addresses a critical care gap: the high early recurrent risk post-ACS. Evidence from trials like HUYGEN,³ PACMAN-AMI,⁴ and SWEDEHEART⁵ confirms that early, intensive LDL-C lowering is safe and effective, championing the “the sooner, the lower, the better” paradigm. The guidelines now mandate proactive, in-hospital initiation of intensive lipid-lowering therapy for all ACS patients (Class I), involving immediate high-intensity statin therapy and the seamless addition of ezetimibe if needed to achieve goal, with all therapy intensified before discharge to maximize risk reduction during the highest-risk post-event period.¹

Personalized strategies for specific populations

The 2025 update introduces key recommendations for specific populations: people with HIV (PWH) aged ≥40 should receive pitavastatin for primary prevention (35% MACE reduction per REPRIEVE);⁶ atorvastatin is recommended for lymphoma patients on anthracyclines to reduce cardiotoxicity (STOP-CA);⁷ high-dose icosapent ethyl (not other omega-3 mixes) is advised for high-risk patients with elevated triglycerides (REDUCE-IT);⁸ and volanesorsen is indicated for familial chylomicronaemia syndrome (FCS) to lower triglycerides and pancreatitis risk.¹

A definitive stance on dietary supplements

In a clear departure from past ambiguity, the update issues a definitive Class III recommendation (i.e., not recommended) against using dietary supplements—including fish oil (except high-dose IPE in specific settings), red yeast rice, and plant sterols—for ASCVD risk reduction. This position, reinforced by trials like SPORT⁹ and OMEMI¹⁰ and EU regulatory actions, emphasizes evidence-based dietary patterns over unproven supplements.

Take-home messages

Towards personalised, early and proactive intensive lipid-lowering management

The 2025 Focused Update endorses a decisive shift in CV prevention, utilising new risk tools (SCORE2, modifiers) for precise stratification, and biomarkers to reclassify risk. The update recommends to initiate intensive lipid lowering treatment early (especially post-ACS), and provides key treatment recommendations for specific populations (for HIV, cancer, statin intolerance). Finally, it recommends against the use of non-evidence-based dietary supplements. The core directive is to personalise care and act earlier, adapting a more intensive lipid-lowering management to reduce ASCVD burden.