ESC 2025 Dyslipidaemia Guidelines – Final Comprehensive Summary
ESC 2025 Dyslipidaemia Guidelines – Final Comprehensive Summary
1. Risk Assessment & Imaging
• SCORE2 & SCORE2-OP (estimate 10-year risk of fatal + non-fatal CV events in adults without CVD or diabetes, guiding prevention intensity) → HeartScore Calculator
(calculated using age, sex, smoking status, systolic blood pressure, and non-HDL or total cholesterol)
• SCORE2: for adults 40–69 years.
• SCORE2-OP: for adults ≥70 years (“Older Persons”).
• Risk thresholds:
• Very high risk: ≥20%
• High risk: 10%–<20%
• Moderate risk: 2%–<10%
• Low risk: <2%
• Refinement tools: In moderate-risk patients, use coronary calcium scoring (CT) or vascular ultrasound (carotid/femoral) (Class IIa).
• If plaques or calcifications are present → risk upgraded (e.g., moderate → high).
(https://www.escardio.org/Education/Practice-Tools/CVD-prevention-toolbox/SCORE-Risk-Charts)
2. Lp(a) – Lipoprotein(a)
• Testing: Once in every adult’s lifetime (levels are genetically determined and stable).
• Threshold: ≥50 mg/dL (≈105 nmol/L) = risk-enhancing factor (Class IIa).
• High Lp(a) can shift patients from moderate → higher risk.
• Repeat testing rarely needed (exceptions: new assay, unclear family history).
3. Risk Modifiers (Class IIa)
• Obstructive sleep apnoea
• Autoimmune inflammatory diseases
• HIV infection
• Physical inactivity
• Preeclampsia, premature menopause, PCOS (in women)
• Elevated Lp(a) ≥50 mg/dL
4. LDL-C Targets
• High/very high risk: <55 mg/dL (unchanged from 2019, Class I).
• Extreme risk: <40 mg/dL (Class IIb), for recurrent vascular events despite maximal therapy or polyvascular disease.
5. Pharmacological Treatments
• Bempedoic acid: Class I, for primary/secondary prevention in statin-intolerant or contraindicated patients.
• Evinacumab (Evkeeza): Monoclonal antibody inhibiting ANGPTL3 (a liver protein that raises TG and LDL-C; blocking it lowers both, even in HoFH).
• Class IIa, for HoFH patients.
• Especially useful when LDL-C targets not reached despite maximal therapy.
• Works independently of PCSK9 and LDL receptor (effective in null mutations).
• Volanesorsen (Waylivra): Antisense drug (blocks mRNA for a protein that impairs triglyceride breakdown).
• Class IIa, only for FCS with severe HTG (>750 mg/dL) to prevent pancreatitis.
• Dose: 300 mg SC weekly.
• Not for general HTG.
• Note: Antisense drugs are short synthetic strands that bind to mRNA and block protein production.
• Pitavastatin: Class I, for HIV patients >40 years (REPRIEVE trial).
6. Gene Therapy vs Antisense Drugs
• Volanesorsen is not gene therapy.
• Antisense oligonucleotides block mRNA temporarily (reversible).
• Gene therapy alters DNA permanently.
7. Combination Therapy
• LDL-C reductions:
• Ezetimibe alone: ~20%
• High-intensity statin + ezetimibe + bempedoic acid + PCSK9 inhibitor: up to ~86%
• Ezetimibe addition recommended routinely (effective, safe, inexpensive).
8. Acute Coronary Syndrome (ACS) Management
• Intensify lipid-lowering therapy before hospital discharge.
• High-intensity statin + ezetimibe; add PCSK9 inhibitor if needed (Class I–IIa).
• Bempedoic acid may substitute if statins contraindicated.
• Avoid stepwise strategy; upfront intensive therapy preferred.
9. Omega-3 & Other Therapies
• Icosapent ethyl (2×2 g/d): Class IIa, in high/very high-risk patients with TG >135 mg/dL; reduces major CV events (REDUCE-IT: –23%).
• Fibrates: Mainly for very severe HTG (≥500–1000 mg/dL) to prevent pancreatitis; not for routine CV risk reduction.
• Inclisiran: Not yet included for primary prevention; awaiting outcomes.
• Supplements (vitamins, red yeast rice, etc.): Not recommended (Class III).
• HDL-C is no longer considered protective.
10. AI & Digital Tools
• ESC Chat: AI chatbot launched in 2025, providing answers directly from ESC guidelines.
• AI promising in coronary CT & vascular Doppler interpretation, reducing cost and expanding personalised care.
11. Comparative Therapies for Hypertriglyceridaemia
• Statins remain the first-line therapy for hypertriglyceridemia, with strongest ASCVD risk reduction evidence.
• Non-statin agents are reserved for persistent or severe TG elevations.
• Fibrates: For very severe HTG (≥500–1000 mg/dL) to prevent pancreatitis; not for routine CV prevention.
• Icosapent ethyl: For high/very high CV risk with TG >135 mg/dL on statins; purified EPA lowering TG and CV events (Class IIa).
• Volanesorsen: For FCS with TG >750 mg/dL; antisense drug blocking mRNA for a protein that impairs TG breakdown (Class IIa).
