A focused update to the dyslipidemia guidelines makes room for new drugs, statins in HIV, and early combo therapy for some.
MADRID, Spain—The European Society of Cardiology and the European Atherosclerosis Society (ESC/EAS) have updated their guidelines for the management of dyslipidemia, and while treatment goals have remained the same, there are some changes to the assessment and classification of patient risk as well as advice for doctors to be more aggressive with some patients.
During the index hospitalization for ACS, the task force recommends intensifying lipid-lowering therapy for patients currently on treatment (class I, level of evidence C) and starting combination therapy with a high-intensity statin plus ezetimibe in treatment-naive patients or those unexpected to get to goal with a statin alone (class IIa, level of evidence C).
“We just want to speed up the process of lowering LDL cholesterol because we know the time is relevant,” Konstantinos Koskinas, MD (University of Bern, Switzerland), co-chair of the focused update, said last week at the ESC Congress 2025. “The earlier we get the LDL to the recommended treatment goals, the better it is for the patient.”
Co-chair François Mach, MD (Geneva University Hospital, Switzerland), said that the goal of using combination therapy in the recently hospitalized ACS patient is to get LDL-cholesterol levels to 55 mg/dL or lower.
The update, which was published in Atherosclerosis and the European Heart Journal, changes only those parts of the dyslipidemia guidelines for which the task force found “significant, substantial, compelling, and practice-changing evidence” that emerged after the 2019 ESC/EAS dyslipidemia guidelines were published, said Koskinas.
LDL Targets Remain the Same
The guidelines have carved out space for newer LDL-lowering therapies, specifically bempedoic acid (Nexletol; Esperion) and evinacumab (Evkeeza; Regeneron). In general, nonstatin therapies with proven cardiovascular benefit, taken alone or in combination, are recommended for patients who can’t take statins (class I, level of evidence A). Bempedoic acid, on the basis of the CLEAR Outcomes trial, is recommended for patients unable to take statins in order to get to LDL goal (class I, level of evidence B).
Ulf Landmesser, MD (Deutsches Herzzentrum Charité, Berlin, Germany), one of the task force members, said bempedoic acid “is a IB recommendation because we have one large outcome trial in this specific population of statin-intolerant patients.”
In the rare group of patients with homozygous familial hypercholesterolemia, evinacumab, a fully human monoclonal antibody inhibitor of angiopoietin-like protein 3, can be considered in those who aren’t at LDL goal despite taking maximum doses of other lipid-lowering therapies (class IIa, level of evidence B).
The earlier we get the LDL to the recommended treatment goals, the better it is for the patient. Konstantinos Koskinas
While the LDL-cholesterol targets have not changed since the 2019 guidelines, the new version provides some direction about when doctors should intervene, particularly for primary prevention. LDL-lowering therapy is recommended in those at very high risk with LDL levels ≥ 70 mg/dL and those at high risk with LDL levels ≥ 100 mg/dL despite nonpharmacologic efforts to lower cholesterol (class I, level of evidence A). Additionally, drug therapy for primary prevention is recommended in the following groups (all class IIa, level of evidence A):
- Very high risk with LDL levels ≥ 55 and < 70 mg/dL
- High risk with LDL levels ≥ 70 and < 100 mg/dL
- Moderate risk with LDL levels ≥ 100 and < 190 mg/dL
- Low risk with LDL levels ≥ 116 and < 190 mg/dL despite nonpharmacologic efforts to lower LDL
“The ESC guidelines, for many years now, and it’s also in the focused update, emphasize the value of optimizing lifestyle before proceeding to any other intervention. By no means are we saying that everyone needs to take a drug to lower his cholesterol levels,” Koskinas said during a press conference. “If a person is able to reach [their] goals without taking a drug, that is excellent, obviously. On the other hand, it is also a fact that many people need to lower their cholesterol levels more intensively in order to have a clinical benefit and really prevent either the first or recurrent event. This often only can be achieved by using drugs or sometimes even combinations of drugs.”
The update recommends estimating patient risk using the SCORE2 and SCORE2-Older Persons (OP) calculators. These tools can estimate the 10-year risk of fatal and nonfatal cardiovascular disease in apparently healthy people as old as 89 years. While new to the dyslipidemia guidelines, SCORE2 and SCORE2-OP have been part of the ESC prevention guidelines since 2021.
In addition to the very-high, high-, moderate-, and low-risk categories, there is a newly created designation of “extreme risk.” These are patients with atherosclerotic cardiovascular disease (ASCVD) who experience recurrent vascular events despite taking maximally tolerated statin therapy and those with disease in multiple arterial beds. In this group, there is a class IIb recommendation to lower LDL cholesterol to less than 40 mg/dL (1 mmol/L).
Like in prior iterations of the guidelines, lipoprotein(a) should be considered a risk modifier when levels exceed 50 mg/dL (105 nmol/L). Beyond this cutoff, physicians can potentially reclassify the patient’s cardiovascular risk category, particularly in those at moderate risk or in those where there might be uncertainty about starting lipid-lowering therapy. Like before, Lp(a) should be measured at least once in a person’s lifetime, usually at the time of the first lipid panel in adulthood, but it can be measured again in postmenopausal women, particularly those with borderline levels.
Special Populations
In patients with hypertriglyceridemia, high-dose icosapent ethyl (Vascepa; Amarin) in combination with statin therapy is now recommended for those at high or very high risk of cardiovascular disease (class IIa, level of evidence B).
Icosapent ethyl is recommended over omega-3 polyunsaturated fatty acids given that STRENGTH showed that an omega-3 carboxylic acid formulation containing both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) didn’t reduce cardiovascular events, said co-chair Jeanine Roeters van Lennep, MD (Erasmus MC University Medical Center, Rotterdam, the Netherlands), during an “Ask the Task Force” session at ESC 2025 devoted to the update.
“That was in contrast with the REDUCE-IT trial that did show a reduction in cardiovascular risk with the pure EPA compound,” she said.
For those with severe hypertriglyceridemia due to familial chylomicronemia syndrome, volanesorsen (Ionis Pharmaceuticals), which is available in Europe but has not been approved by the US Food and Drug Administration, gained a class IIa (level of evidence B) recommendation.
On the basis of the REPRIEVE trial, statins now have a class I (level of evidence B) recommendation for use in people ages 40 years and older with HIV but without preexisting cardiovascular disease. Statin therapy should be started irrespective of baseline cardiovascular risk and LDL cholesterol levels, with the choice of statin dictated by possible drug-drug interactions. The heightened risk of developing ASCVD in patients with HIV was acknowledged in the 2019 guidelines, but statin therapy was recommended only for those with dyslipidemia, said Roeters van Lennep.
“Now, the recommendation is much broader,” she said.
Statins should also be considered for adults at risk of developing chemotherapy-related toxicity (class IIa, level of evidence B), a recommendation based on four randomized trials showing the cardioprotective effects of statins in cancer patients receiving anthracycline-based treatments. The ESC cardio-oncology guidelines contain the same recommendation.
And finally, the ESC/EAS task force emphasizes that dietary supplements or vitamins without proven LDL-lowering efficacy are not to be used to lower the risk of ASCVD. That recommendation is supported by data from the SPORT trial, which found commonly used supplements—fish oil, cinnamon, garlic, turmeric, plant sterols, and red yeast rice—couldn’t beat statin therapy for LDL cholesterol-lowering.