ESC 2025 Update

Treatment Recommendations (2025 Update)

Clinical summary of the latest ESC guidelines for lipid-lowering therapies and cardiovascular disease prevention.

Extreme Risk (ESC 2025)

Patient Profile: Patients with ASCVD who experience recurrent vascular events while on maximally tolerated statin-based therapy, polyvascular disease (≥2 arterial territories), ACS with multivessel coronary disease, or familial hypercholesterolemia with established ASCVD.

LDL-C Goal: LDL-C < 1.0 mmol/L (< 40 mg/dL) — the most aggressive target.

Treatment Strategy

Class IIb

Consider lower LDL-C goal < 1.0 mmol/L (< 40 mg/dL) for patients meeting extreme risk criteria.

Class I

Intensify lipid-lowering therapy during hospitalization for acute events.

Class IIa

Start high-intensity statin + ezetimibe immediately if goal unlikely with statin alone.

Class IIa

Add PCSK9 inhibitor if LDL-C remains above target despite maximum statin + ezetimibe.

Very High Risk: Secondary Prevention

Patient Profile: Individuals with documented ASCVD (clinical or imaging).

LDL-C Goal: LDL-C < 1.4 mmol/L (< 55 mg/dL) AND ≥50% reduction from baseline.

Treatment Strategy

Class I

Lifestyle modification and concomitant lipid-lowering drug intervention regardless of baseline untreated LDL-C levels.

Class I

Post-ACS Acute Phase: Intensification of lipid-lowering therapy during index hospitalization for patients already on prior therapy.

Class IIa

Post-ACS Treatment-Naïve: Initiating combination therapy (high-intensity statin + ezetimibe) during index hospitalization if expected not to achieve goal with statin alone.

Very High Risk: Primary Prevention

Patient Profile: Severe CKD (eGFR <30), SCORE2 ≥20%, FH with major risk factor, or DM with target organ damage / ≥3 risk factors.

LDL-C Goal: LDL-C < 1.4 mmol/L (< 55 mg/dL) AND ≥50% reduction from baseline.

Treatment Strategy

Class I

Pharmacological therapy if untreated LDL-C is ≥ 1.8 mmol/L (70 mg/dL).

Class IIa

Pharmacological therapy if untreated LDL-C is between 1.4 and < 1.8 mmol/L (55 to < 70 mg/dL).

High Risk: Primary Prevention

Patient Profile: SCORE2 10–20%, moderate CKD, FH (no other risk factors), DM duration ≥10 years, or single extremely elevated risk factor (e.g. TC >8.0, BP ≥180/110).

LDL-C Goal: LDL-C < 1.8 mmol/L (< 70 mg/dL) AND ≥50% reduction from baseline.

Treatment Strategy

Class I

Pharmacological therapy if untreated LDL-C is ≥ 2.6 mmol/L (100 mg/dL).

Class IIa

Pharmacological therapy if untreated LDL-C is between 1.8 and < 2.6 mmol/L (70 to < 100 mg/dL).

Moderate Risk: Primary Prevention

Patient Profile: SCORE2 2–10%, or young DM patients (<10 years duration, no other factors).

LDL-C Goal: LDL-C < 2.6 mmol/L (< 100 mg/dL).

Risk Modifiers: Consider subclinical coronary atherosclerosis imaging (CAC score) to upgrade risk classification.

Treatment Strategy

Class I

Lifestyle modification target.

Class IIa

Pharmacological therapy if untreated LDL-C is ≥ 2.6 mmol/L (100 mg/dL).

Low Risk: Primary Prevention

Patient Profile: SCORE2 < 2%.

LDL-C Goal: LDL-C < 3.0 mmol/L (< 116 mg/dL).

Treatment Strategy

Class I

Lifestyle advice is the primary intervention.

Class IIb

Pharmacological therapy if untreated LDL-C ≥ 3.0 mmol/L despite lifestyle optimization.

Key Pharmacological Updates for Refractory Patients

Bempedoic Acid

Class I

Recommended for patients who are unable to take statin therapy to achieve their LDL-C goal.

Bempedoic Acid Combination

Class IIa

Add to maximally tolerated statin (with/without ezetimibe) for high/very high risk patients not at goal.

Evinacumab

Class IIa

For patients ≥5 years old with homozygous FH not at goal despite maximum therapies.

Disclaimer: This reference page summarises the ESC 2025 CVD prevention and treatment updates. It does not replace the full guideline document. Clinical decisions should always be made in context of the individual patient.