The European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) have released updated recommendations on the management of dyslipidaemia. The guidance presented at the ESC 2025 Congress and published in the European Heart Journal replaces the 2019 version and reflects a stronger focus on individual cardiovascular (CV) risk estimation.

Among the notable changes, the role of imaging was reinforced in CV risk assessment to detect atherosclerosis and measure the coronary calcium score in asymptomatic patients at moderate risk (Class IIa). Experts set a lipoprotein(a) — [Lp(a)] — threshold of 50 mg/dL (105 nmol/L), above which Lp(a) should be considered a CV risk-enhancing factor (Class IIa).

In terms of treatment, bempedoic acid (Nilemdo, Nustendi) is now recommended for primary and secondary prevention, particularly in patients with statin intolerance or contraindications (Class I).

Evinacumab (Evkeeza), a recombinant human monoclonal antibody that binds to and inhibits angiopoietin-like 3 (ANGPTL3), should be considered for the treatment of homozygous familial hypercholesterolaemia, and volanesorsen, an antisense drug (Waylivra), for severe hypertriglyceridaemia associated with familial chylomicronemia syndrome (Class IIa).

This edition of the ESC Congress also launched ESC Chat, an artificial intelligence (AI)-based chatbot that answers clinicians’ questions by drawing exclusively on ESC clinical practice guidelines; this tool is available in a mobile version.

New Risk Scores

First introduced in 2021, the SCORE2 and SCORE2-OP algorithms were confirmed in the guidelines. They estimated the 10-year risk for CV events in individuals without established CV disease or diabetes (Class I).

Revised thresholds for CV risk are as follows:

• Very high risk: SCORE2 or SCORE2-OP ≥ 20%
• High risk: SCORE2 or SCORE2-OP 10% to < 20%
• Moderate risk: SCORE2 or SCORE2-OP 2% to < 10%
• Low risk: SCORE2 or SCORE2-OP < 2%

For patients classified as moderate risk by SCORE2 or SCORE2-OP, consider coronary artery calcium score derived from a noncontrast CT scan or carotid or femoral plaque detection by vascular ultrasound to refine risk classification (Class IIa, Level B).

Risk Modifiers

Speaking with Medscape’s French edition, Pierre Sabouret, MD, a leading cardiologist from Sorbonne Université, Paris, France, emphasised, “The use of SCORE2 remains of interest at the population level, while the use of imaging allows for better definition of risk at the individual level.”

He believes that “the role of imaging is progressing, but not yet sufficiently, certainly for medical economic reasons.”

Experts are increasingly supporting personalised risk assessment. They highlighted several risk modifiers that should be considered in patients with moderate CV risk to refine the classification (Class IIa).

This approach can be particularly useful when deciding whether therapeutic intervention is warranted.

The modifiers include obstructive sleep apnoea, chronic inflammatory autoimmune diseases, HIV infection, physical inactivity, preeclampsia, premature menopause, and polycystic ovary syndrome in women. Patients with elevated Lp(a) levels above 50 mg/dL were also included.

“Epidemiological data show that risk assessment using SCORE2 and SCORE2-OP is not satisfactory in certain patient subpopulations, particularly younger patients,” emphasised Sabouret.

“Patients who appear to be at moderate risk but have a risk modifier should be able to benefit from imaging to better define the risk and help decide whether to treat or not,” he said.

Low-Density Lipoprotein Cholesterol (LDL-C)

LDL-C levels of < 40 mg/dL have been proposed for patients classified as having extreme risk in recent ESC/EAS recommendations.

According to Sabouret, the risk modifiers are well defined, but it remains unclear how they are considered in practice.

With Lp(a), if levels rise progressively above 50 mg/dL, “cardiologists do not have precise guidance on the strategy to follow,” depending on the level measured.

AI Imaging

“To achieve a more favourable cost-benefit ratio with an individual assessment based more on imaging, we could rely on artificial intelligence to help interpret the images. Experimentation with an AI tool has already proven effective in analysing coronary CT and vascular Doppler results. Therefore, we can hope to have more imaging at a lower cost,” said Sabouret.

LDL Targets

LDL-C targets for high-risk patients remain unchanged. The 2019 recommendations had significantly lowered the targets, notably to LDL-C < 55 mg/dL in very high-risk patients (Class I, Level A). These targets drew debate, with some experts considering them unrealistic.

A new threshold of LDL-C < 40 mg/dL may be considered (Class IIb) for patients at extreme CV risk, defined as those with confirmed atherosclerosis and recurrent vascular events despite intensive treatment at the maximum tolerated dose, or those with polyvascular atherosclerosis.

“That said, in patients who have a recurrence of ischemic stroke with an LDL-C < 55 mg/dL, the primary target is often not LDL-C, but rather other poorly controlled factors,” said Sabouret.

Combinations

When lifestyle measures such as diet, exercise, diabetes control, and smoking cessation fail, lipid-lowering treatment is recommended for primary prevention in very high-risk patients with LDL-C ≥ 70 mg/dL and high-risk patients with LDL-C ≥ 100 mg/dL (Class I).

Bempedoic acid is recommended for primary or secondary prevention in patients who are intolerant to or have contraindications to statins.

In those at high or very high CV risk, it can be added to maximally tolerated statin treatment with or without ezetimibe to help achieve LDL-C targets (Class IIa).

For patients with homozygous familial hypercholesterolemia aged 5 years or older who cannot reach LDL-C goals despite optimised treatment, including a statin, ezetimibe, and a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (evinacumab), an ANGPTL3 inhibitor may be considered (Class IIa).

Experts have noted that several combinations of lipid-lowering treatments have proven effective in reducing LDL-C levels.

According to the guidelines, reductions range from approximately 20% with ezetimibe alone to 86% with a combination of high-intensity statins, ezetimibe, bempedoic acid, and PCSK9 inhibitors.

“We can more easily achieve our goals with lipid-lowering combinations, particularly by combining a statin at the maximum tolerated dose with ezetimibe, which I now routinely add because it is effective, well-tolerated, and inexpensive,” emphasised Sabouret. “The addition of ezetimibe allows for an additional 20% reduction in LDL-C.”

Patients With HIV

For patients with HIV, pitavastatin is recommended for primary prevention in those aged > 40 years (Class I). This is based on the REPRIEVE study, which showed a 35% reduction in the risk for major CV events.

Patients with cancer receiving anthracycline-based chemotherapy with high or very high CV risk should also be considered for statin therapy for primary prevention (Class IIa), in line with cardio-oncology guidelines.

Sabouret noted that some lipid-lowering drugs are not yet widely available in France. Bempedoic acid “should be on the market this year,” while access to PCSK9 inhibitors remains limited due to ongoing negotiations between suppliers and the government.

When asked about overmedication, Konstantinos Koskinas, MD, a cardiologist at Bern University Hospital, Bern, Switzerland, and coauthor of the new recommendations, emphasised that lifestyle, nutrition, and exercise remain essential. But if that is not enough, we now have many medications that we can combine to achieve the goals.

Acute Coronary Syndrome (ACS) Management

Treatment intensification is recommended for secondary prevention in patients hospitalised with ACS. Patients already on lipid-lowering therapy should add ezetimibe or a PCSK9 inhibitor when statins are at their maximum tolerated dose (Class I).

In patients naive to lipid-lowering treatment before ACS, high-intensity statins combined with ezetimibe should be considered before hospital discharge if statins alone are insufficient (Class IIa). Bempedoic acid may be substituted for statins in these regimens.

“In these patients, we now prefer intensive treatment from the outset before hospital discharge rather than a stepwise approach,” Sabouret emphasised.

“The SANTORINI study showed that only 20% of post-ACS patients reach LDL-C < 55 mg/dL with a stepwise strategy.”

Food Supplements

The latest guidelines do not include the PCSK9 inhibitor inclisiran for the prevention of CV risk, despite FDA approval for primary prevention in addition to statins. However, its use is limited because its long-term morbidity and mortality outcomes remain unclear. In secondary prevention, “we are awaiting the morbidity and mortality results of studies,” particularly ORION-4 and VICTORION-2P, noted Sabouret.

For hypertriglyceridaemia, high-dose icosapent ethyl (2 × 2 g/d), an omega-3 derivative, should be considered in addition to statin treatment in high- or very high-risk patients with triglycerides > 135 mg/dL (Class IIa).

The REDUCE-IT trial reported a 23% reduction in major CV events after a median follow-up of nearly 5 years.

Volanesorsen, an antisense oligonucleotide, may be considered to prevent pancreatitis (300 mg/wk subcutaneously, Class IIa) in patients with severe hypertriglyceridaemia (> 750 mg/dL) due to the familial chylomicronemia syndrome.

Guidelines recommend against using food supplements or vitamins to lower CV risk, as their benefits are considered insufficient (Class III). This includes red yeast rice, which contains lovastatin and may cause adverse effects.

Additionally, “HDL [high-density lipoprotein] is no longer considered a protective factor” and is no longer included as a CV risk modifier.

This story was translated from Medscape’s French edition.