Dyslipidemias include elevated low-density lipoprotein (LDL) cholesterol, triglycerides, or lipoprotein(a). The primary goal of management is to prevent atherosclerotic cardiovascular disease (ASCVD). In today's side-by-side guideline comparison, we will review recommendations for non-statin medication used to lower LDL-cholesterol. You are encouraged to review the full text guidelines, which can be found at the links below, for a more comprehensive understanding of the most recent evidence-based clinical practice recommendations on the management of dyslipidemia.
For this dyslipidemia guidelines side-by-side comparison, we feature the latest clinical practice guidelines from the American Association of Clinical Endocrinologists (AACE), the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) and the American College of Cardiology (ACC)/American Heart Association (AHA) on dyslipidemia.
| Item | American Association of Clinical Endocrinology Clinical Practice Guideline on Pharmacologic Management of Adults With Dyslipidemia | 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias: Developed by the task force for the management of dyslipidaemias of the European Society of Cardiology and the European Atherosclerosis Society | 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/ AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines |
|---|---|---|---|
| Authoring Organization | American Association of Clinical Endocrinologists | European Society of Cardiology/European Atherosclerosis Society | American College of Cardiology/American Heart Association |
| Publication Date | February 2025 | August 2025 | March 2026 |
| Graded Recommendations | Yes | Yes | Yes |
| Links | Summary / Full Text | Overview / Full Text | Summary / Full Text |
Key Takeaways From the Side-by-Side Comparison
General:
- The AACE guideline has a limited scope focusing on newer non-statin pharmacotherapy for dyslipidemia.
- The ESC/EAS guideline is a focused update on the management of dyslipidemias. Recommendations were made for cardiovascular risk estimation, low-density lipoprotein (LDL) lowering with bempedoic acid and evinacumab, lipid-lowering during index hospitalization, lipoprotein(a), pharmacotherapy for hypertriglyceridemia, statin therapy for patients with HIV and cancer, and dietary supplements.
- The ACC/AHA guideline is the most comprehensive of the three with recommendations addressing evaluation, management, and monitoring of dyslipidemia which includes high blood cholesterol, hypertriglyceridemia, and high lipoprotein(a). Management components included primary prevention, severe hypercholesterolemia, hypercholesterolemia in patients with diabetes, clinical ASCVD, subclinical atherosclerosis, and hypertriglyceridemia. Special management considerations are included for elevated Lipoprotein(a), dyslipidemia in children, young adults, and older adults, pregnant or lactating patients, patients with heart failure, chronic inflammatory diseases, chronic kidney disease, HIV, and statin-attributed muscle symptoms.
ASCVD Risk:
- The AACE recommends ASCVD risk be assessed using a validated tool, but did not prefer any one tool over another.
- The ESC/EAS recommends using risk scores like SCORE2 and SCORE2-OP to estimate cardiovascular risk. These calculators are intended for European patients aged 40-69 years who do not have diabetes.
- The ACC/AHA guideline recommends PREVENT-ASCVD equations for certain individuals depending on age, ASCVD status, presence of subclinical atherosclerosis, comorbid diabetes, and LDL-cholesterol and/or triglyceride levels.
- Both the SCORE2 and PREVENT risk calculators estimate risk based on age, sex, systolic blood pressure, total cholesterol, high-density lipoprotein (HDL), and smoking status. Additionally, PREVENT takes into consideration estimated glomerular filtration rate (eGFR), body mass index (BMI), history of diabetes, and current use of lipid-lowering or antihypertensive medications. PREVENT is recommended beginning at age 30 whereas SCORE2 is recommended beginning at the age of 40 years.
- For individuals with heterozygous familial hypercholesterolemia (HeFH) the ACC/AHA recommends not using standard risk assessment tools since those are designed to calculate risk in the general population.
- The ACC/AHA also recommends measurement of lipoprotein(a) at least once for ASCVD risk assessment and potentially apolipoprotein B (apoB) measurement to improve risk assessment. The AACE found there to be limited use for these measurements in calculating ASCVD risk.
Risk Enhancers:
- The AACE did not address risk enhancers with any clinical recommendations finding that adding risk enhancers to a standard, validated ASCVD risk calculator offered little improvement in risk prediction.
- Both the EAS/ESC and the ACC/AHA recommend taking risk modifiers into consideration, including coronary artery calcium (CAC) scores. This is particularly helpful in guiding treatment decisions in patients with borderline risk.
Treatment Goals:
- The AACE suggests treating LDL-cholesterol to less than 70 mg/dL in patients with ASCVD or at increased risk of ASCVD.
- Both the EAS/ESC and the ACC/AHA recommends treatment goals based on estimated risk for ASCVD as follows:
- Moderate/intermediate risk: LDL-cholesterol goal less than 100 mg/dL.
- High risk: LDL-cholesterol goal less than 70 mg/dL.
- The EAS/ESC also recommends less aggressive LDL goals for low risk patients and more aggressive LDL goals for patients at very high risk.
Non-Statin Lipid-Lowering Therapy:
Ezetimibe
- Neither the AACE nor the EAS/ESC addressed the use of ezetimibe.
- The ACC/AHA guideline recommends adding ezetimibe to a maximally tolerated statin for patients with:
- Severe hypercholesterolemia with ASCVD
- Severe hypercholesterolemia without ASCVD but with HeFH, additional ASCVD risk factors or coronary calcification
- Clinical ASCVD who are at very high risk.
- The ACC/AHA guideline states that it may be reasonable to add ezetimibe to a maximally tolerated statin for patients with:
- High 10-year ASCVD risk
- Clinical ASCVD who are not at very high risk
- Confirmed homozygous familial hypercholesterolemia (HoFH).
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Monoclonal Antibodies (mAbs)
- The AACE suggests adding a PCSK9 mAb for patients on a maximally tolerated statin who have ASCVD or are at increased risk for ASCVD, but suggests against PCSK9 mAb use in patients without ASCVD who can tolerate other lipid-lowering therapies.
- The EAS/ESC did not address the use of PCSK9 mAbs.
- The ACC/AHA guideline recommends adding a PCSK9 mAb to a maximally tolerated statin for patients with:
- Severe hypercholesterolemia with ASCVD
- Severe hypercholesterolemia without ASCVD but with HeFH, additional ASCVD risk factors or coronary calcification
- Clinical ASCVD who are at very high risk.
- The ACC/AHA guideline states that it may be reasonable to add a PCSK9 mAb to a maximally tolerated statin for patients with:
- High 10-year risk whether or not they are also taking ezetimibe
- Clinical ASCVD who are not at very high risk
- Confirmed HoFH.
Bempedoic Acid
- The AACE suggests against using bempedoic acid for patients without ASCVD who may tolerate other lipid-lowering medications.
- Both the EAS/ESC and ACC/AHA suggest considering adding bempedoic acid to a maximally tolerated statin with or without ezetimibe for patients at high or very high risk.
- The ACC/AHA guideline also recommends adding bempedoic acid to a maximally tolerated statin for patients with:
- Severe hypercholesterolemia with ASCVD
- Severe hypercholesterolemia without ASCVD but with HeFH, additional ASCVD risk factors, or coronary calcification.
- THe ACC/AHA guideline states that it may be reasonable to add bempedoic acid to a maximally tolerated statin for patients with:
- High 10-year risk whether or not they are also taking ezetimibe
- Confirmed HoFH
- Clinical ASCVD who are at very high risk with or without ezetimibe and/or PCSK9 mAb
- Clinical ASCVD who are not at very high risk.
Inclisiran
- The AACE cited insufficient evidence to make a recommendation for or against the use of inclisiran.
- The EAS/ESC did not address the use of inclisiran.
- The ACC/AHA guideline states that it is reasonable to add inclisiran to a maximally tolerated statin with or without ezetimibe for patients with:
- Severe hypercholesterolemia with or without ASCVD
- Clinical ASCVD at very high risk, who can not tolerate a PCSK9 mAb.
Evinacuma
- The AACE did not address the use of evinacumab for dyslipidemia.
- Both the EAS/ESC and ACC/AHA consider adding evinacumab to maximally tolerated lipid-lowering therapies for patients with HoFH. The EAS/ESC specifically recommends this for patients with HoFH who are at least 5 years old.
Lomitapide
- The AACE and the EAS/ESC did not address the use of lomitapide.
- The ACC/AHA considers the addition of lomitapide in patients with HoFH on a maximally tolerated statin, ezetimibe, and a PCSK9 mAb.
Dietary Supplements
- The AACE did not address the use of dietary supplements for elevated LDL-cholesterol.
- Neither the EAS/ESC nor the ACC/AHA recommend dietary supplements to lower the risk of ASCVD.
Comparison of Recommendations
Assessment of ASCVD Risk and Treatment Goals:
| Type | AACE | ACC/AHA | EAS/ESC |
|---|---|---|---|
| ASCVD Risk Assessment | For primary prevention in adults with dyslipidemia, AACE recommends for the use of a validated tool or calculator to predict future risk of ASCVD events as part of shared decision-making around treatment. | In adults aged 30 to 79 years without ASCVD or subclinical atherosclerosis and with an LDL-C level between 70 and 189 mg/dL (1.8-4.9 mmol/L), the PREVENT-ASCVD equations should be used to estimate 10-year ASCVD risk, with categorization as having low (<3%), borderline (3% to <5%), intermediate (5% to <10%), or high (≥10%) risk. In adults aged 40 to 75 years without a history of ASCVD or diabetes who have persistently elevated TG levels ≥150 to 499 mg/dL (≥1.7-5.6 mmol/L), it is recommended to estimate 10-year ASCVD risk by the PREVENT equations to guide a benefit-risk discussion regarding further optimization of diet and lifestyle management as well as the potential initiation of statin therapy to reduce ASCVD risk. In individuals with HeFH, standard risk assessment tools developed for the general population should not be used to calculate 10- or 30-year ASCVD risk. In adults and children who have undergone a standard lipid profile, reporting of non–HDL-C is recommended for ASCVD risk assessment and to guide initiation and monitoring of LLT. In all adults, measurement of Lp(a) concentration is recommended at least once for ASCVD risk assessment. In adults not on LLT, measurement of apoB may be reasonable to enhance ASCVD risk assessment, guide decisions about initiation of LLT, and characterize inherited lipid disorders. | SCORE2 is recommended in apparently healthy people <70 years of age without established ASCVD, DM, CKD, genetic/rare lipid or BP disorders for estimation of 10-year fatal and non-fatal CVD risk. SCORE2-OP is recommended in apparently healthy people ≥70 years of age without established ASCVD, DM, CKD, genetic/rare lipid or BP disorders for estimation of 10-year fatal and non-fatal CVD risk. |
| Risk Enhancers | Not addressed. | In adults without ASCVD with a borderline 10-year ASCVD risk estimate (3% to <5%) by the PREVENT-ASCVD equations, consideration of risk enhancers is reasonable to personalize risk assessment and the potential benefit of initiating LLT as an adjunct to lifestyle management to reduce ASCVD risk. In adults without ASCVD with a borderline 10-year ASCVD risk estimate (3% to <5%) by the PREVENT-ASCVD equations, if hsCRP is measured and is ≥2 mg/L on 2 successive occasions with no identifiable underlying cause of hsCRP elevation, high-intensity statin therapy can be useful to reduce the risk of ASCVD events. In adults without ASCVD, consideration of reproductive risk markers, such as early menopause (<45 years old) and history of adverse pregnancy outcomes (gestational hypertension, preeclampsia, gestational diabetes, preterm delivery) is reasonable to personalize ASCVD risk assessment when considering the potential benefit of initiating LLT as an adjunct to lifestyle management for primary ASCVD prevention. In adults at intermediate risk and select adults at borderline risk with no prior ASCVD, if the decision regarding LLT remains uncertain, a CAC score should be used for further risk stratification and to guide the decision to withhold, postpone, or initiate therapy. | Risk modifiers should be considered in individuals at moderate risk or individuals around treatment decision thresholds to improve risk classification. Presence of subclinical coronary atherosclerosis by imaging or increased CAC score by CT should be considered as risk modifiers in individuals at moderate risk or individuals around treatment decision thresholds to improve risk classification. |
| Treatment Goals: LDL-C Reduction | In adults undergoing treatment for dyslipidemia who have ASCVD or are at increased risk for ASCVD, AACE suggests for treatment to an LDL-C target of <70 mg/dL. | In adults at borderline (3% to <5%) or intermediate (5% to <10%) 10-year estimated risk for ASCVD in whom statin therapy is initiated, it is reasonable to treat to a goal of LDL-C <100 mg/dL (2.6 mmol/L) and non–HDL-C <130 mg/dL (3.4 mmol/L) to reduce ASCVD risk. In adults at high (≥10%) 10-year risk for ASCVD in whom a decision to initiate statin therapy is made, it is reasonable to treat to a goal of LDL-C <70 mg/dL (1.8 mmol/L) and non–HDL-C <100 mg/dL (2.6 mmol/L) to reduce ASCVD risk. | In individuals at moderate risk, an LDL-C goal of <2.6 mmol/L (<100 mg/dL) should be considered. In patients at high risk, an LDL-C reduction of ≥ 50% from baseline and an LDL-C goal of <1.8 mmol/L (<70 mg/dL) are recommended. In primary prevention for individuals with FH at very-high risk, an LDL-C reduction of ≥ 50% from baseline and an LDL-C goal of <1.4 mmol/L (<55 mg/dL) should be considered. In primary prevention for individuals at very-high risk but without FH, an LDL-C reduction of ≥ 50% from baseline and an LDL-C goal of <1.4 mmol/L (<55 mg/dL) are recommended. For patients with ASCVD who experience a second vascular event within 2 years (not necessarily of the same type as the first event) while taking maximally tolerated statin-based therapy, an LDL-C goal of <1.0 mmol/L (<40 mg/dL) may be considered. In individuals at low risk, an LDL-C goal <3.0 mmol/L (<116 mg/dL) may be considered. |
Non-Statin Lipid Lowering Therapies:
| Treatment | AACE | EAS/ESC | ACC/AHA |
|---|---|---|---|
| Ezetimibe, PCSK9 mAbs (evolocumab, alirocumab), Bempedoic Acid | Ezetimibe not addressed. In adults with dyslipidemia who do not have ASCVD and can tolerate other lipid-lowering medications, AACE suggests against the use of bempedoic acid in addition to usual care. NEXT In adults with dyslipidemia who do not have ASCVD and who may tolerate other lipid-lowering medications, AACE suggests against the use of evolocumab or alirocumab in addition to usual care. In adults with dyslipidemia who are on maximally tolerated statins and have ASCVD or are at increased risk for ASCVD but who are not at goal (LDL-C <70 mg/dL), AACE suggests for the use of evolocumab or alirocumab in addition to usual care. | Ezetimibe not addressed. The addition of bempedoic acid to the maximally tolerated dose of statin with or without ezetimibe should be considered in patients at high or very high risk in order to achieve the LDL-C goal. | In adults at high (≥10%) 10-year estimated risk for ASCVD on maximally tolerated statin, it is reasonable to add ezetimibe if a goal LDL-C <70 mg/dL (1.8 mmol/L) and non–HDL-C <100 mg/dL (2.6 mmol/L) is not achieved. In adults at high (≥10%) 10-year estimated risk for ASCVD on maximally tolerated statin with or without ezetimibe, it may be reasonable to add a PCSK9 mAb or bempedoic acid if a goal of LDL-C <70 mg/dL (1.8 mmol/L) and non–HDL-C <100 mg/dL (2.6 mmol/L) is not achieved to lower LDL-C and reduce ASCVD risk. In adults with severe hypercholesterolemia with an LDL-C ≥190 mg/dL (4.9 mmol/L) and without clinical ASCVD, additional ASCVD risk factors, HeFH, or subclinical atherosclerosis who are on maximally tolerated statin therapy, the addition of ezetimibe, a PCSK9 mAb and/or bempedoic acid is recommended to achieve a goal of LDL-C <100 mg/dL (2.6 mmol/L) and a non–HDL-C goal of <130 mg/dL (3.4 mmol/L) and to reduce ASCVD risk. In adults with severe hypercholesterolemia with LDL-C ≥190 mg/dL (4.9 mmol/L) without clinical ASCVD but with clinical or genetic confirmation of HeFH, additional ASCVD risk factors, or documented coronary calcification, who are on maximally tolerated statin therapy, the addition of ezetimibe, a PCSK9 mAb and/or bempedoic acid to achieve a goal of LDL-C <70 mg/dL (1.8 mmol/L) and non–HDL-C <100 mg/dL (2.6 mmol/L) is recommended to lower LDL-C and reduce ASCVD risk. In adults with severe hypercholesterolemia with LDL-C ≥190 mg/dL (4.9 mmol/L) with clinical ASCVD, who are on maximally tolerated statin therapy, the addition of ezetimibe, a PCSK9 mAb, or bempedoic acid is recommended to achieve a goal of LDL-C <55 mg/dL (1.4 mmol/L) and non–HDL-C <85 mg/dL (2.2 mmol/L) to lower LDL-C and reduce ASCVD risk. In adults with clinical or genetic confirmation of HoFH currently on maximally tolerated statin therapy, the addition of ezetimibe, PCSK9 mAb, and/or bempedoic acid is reasonable to lower LDL-C. In adults with clinical ASCVD who are not at very high risk and on maximally tolerated statin therapy, it is reasonable to add ezetimibe, a PCSK9 mAb, or bempedoic acid (selection depending on degree of LDL-C lowering needed and patient preference) to achieve a goal of LDL-C <70 mg/dL (1.8 mmol/L) and non–HDL-C <100 mg/dL to reduce the risk of ASCVD events. In adults with clinical ASCVD who are at very high risk on maximally tolerated statin therapy, it is reasonable to add bempedoic acid to a statin, with or without ezetimibe and/or PCSK9 mAb, to reach an LDL-C goal <55 mg/dL (1.4 mmol/L) and non–HDL-C <85 mg/dL (2.2 mmol/L) to reduce the risk of ASCVD events. In adults with clinical ASCVD who are at very high risk and on maximally tolerated statin therapy, ezetimibe and/or a PCSK9 mAb should be added (selected based on the degree of LDL-C lowering needed and patient preference) to achieve a goal of LDL-C <55 mg/dL (1.4 mmol/L) and non–HDL-C <85 mg/dL (2.2 mmol/L) and to reduce risk of ASCVD events. |
| Inclisiran | There is insufficient evidence to make a recommendation for or against the use of inclisiran. | Not addressed. | In adults with severe hypercholesterolemia with or without clinical ASCVD and LDL-C ≥100 mg/dL (2.6 mmol/L) despite maximally tolerated statin with or without ezetimibe therapy, treatment with inclisiran is reasonable to lower LDL-C. In adults with clinical ASCVD who are at very high risk and on maximally tolerated statin therapy with or without ezetimibe, it is reasonable to add inclisiran in those unable to tolerate or obtain evolocumab or alirocumab or have a strong preference for less frequent dosing to achieve an LDL-C goal <55 mg/dL (1.4 mmol/L) and non–HDL-C <85 mg/dL (2.2 mmol/L). |
| Evinacumab | Not addressed. | Evinacumab should be considered in patients with homozygous familial hypercholesterolaemia aged 5 years or older who are not at LDL-C goal despite receiving maximum doses of lipid-lowering therapy to lower LDL-C levels. | In adults with clinical or genetic confirmation of HoFH currently on maximally tolerated statin therapy, ezetimibe, and PCSK9 mAb with an LDL-C ≥100 mg/dL (2.6 mmol/L), the addition of evinacumab may be reasonable to lower LDL-C. |
| Lomitapide | Not addressed. | Not addressed. | In adults with clinical or genetic confirmation of HoFH currently on maximally tolerated statin therapy, ezetimibe, and PCSK9 mAb with LDL-C ≥100 mg/dL (2.6 mmol/L), the addition of lomitapide with regular monitoring for hepatic safety may be reasonable to lower LDL-C. |
| Dietary Supplements | Not addressed. | Dietary supplements or vitamins without documented safety and significant LDL-C-lowering efficacy are not recommended to lower the risk of ASCVD. | In individuals with dyslipidemia, the use of dietary supplements is not recommended to lower LDL-C or TG based on limited and inconsistent data and/or limited benefits in lipid-lowering and reduction in ASCVD risk. |
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