Introduction

Definitions and Classifications

Evaluation and Diagnosis

Management

Complications of Management

Design and created by Guideline Central in participation with the American College of Cardiology and American Heart Association.

Management of Dyslipidemia

American College of Cardiology

American Heart Association

Publication Date: March 13, 2026

Treat dyslipidemia earlier to reduce lifelong risk of prolonged exposure to atherogenic lipoproteins. Health behavior counseling to support lifestyle optimization should start in youth, with early consideration of pharmacotherapy in youth with familial hypercholesterolemia (FH) and in young adulthood in individuals with low-density lipoprotein-cholesterol (LDL-C) ≥160 mg/dL or a strong family history of premature atherosclerotic cardiovascular disease (ASCVD).
Use the more contemporary American Heart Association Predicting Risk of cardiovascular disease EVENTs (PREVENT™) equations instead of the older Pooled Cohort Equations (PCE) for 10- and 30-year risk assessment to guide lipid-lowering therapy (LLT) in primary prevention in adults aged 30 to 79 years. Use the “CPR” Model:
1. Calculate 10-year ASCVD risk;
2. Personalize the estimated risk to the specific patient by considering factors not included in PREVENT-ASCVD equations; and
3. possibly Reclassify with selective use of coronary artery calcium (CAC) and Reassess treatment recommendations.
LDL-lowering therapy can be considered in adults for primary prevention of ASCVD with a 10-year PREVENT-ASCVD risk estimate of 3% to <5% (borderline risk) and should be considered for those at 5% to <10% (intermediate risk) 10-year risk after a clinician-patient discussion.
LDL-C and non–HDL-C treatment goals are back to guide LLT. Percentage reduction in LDL-C remains a priority for all individuals as well, with goal for % reduction depending on the level of ASCVD risk.
Apolipoprotein B (ApoB) testing can be useful to improve risk assessment and guide therapy once LDL-C and non–HDL-C goals are met, particularly in those with elevated triglycerides (TG) (>200 mg/dL), diabetes, or low achieved LDL-C (<70 mg/dL). ApoB measurement helps identify adults with residual elevated lipoprotein-related risk that may be underestimated by the standard lipid profile alone and may be useful in the diagnosis of specific lipid and lipoprotein disorders.
Lipoprotein(a) [Lp(a)] should be measured at least once to identify those individuals at higher risk of ASCVD. It is considered as a risk-enhancing factor at levels ≥125 nmol/L (50 mg/dL), which is associated with about a 1.4-fold increased ASCVD risk, and values ≥250 nmol/L (100 mg/dL) are associated with ≥2-fold higher estimated risk. The presence of elevated Lp(a) should be an indication for more intensified LDL-C lowering and management of other risk factors.
Coronary artery calcium (CAC) scoring in men at least 40 years of age and women at least 45 years of age can improve risk assessment and guide LDL-C and non–HDL-C goals. Both the absolute amount of CAC and the corresponding standardized percentile (currently based on age, sex, and race) have prognostic importance and help to reclassify risk in adults.
LDL-lowering therapy is recommended for primary prevention in adults aged 40 to 75 years with diabetes, chronic kidney disease stage 3 or 4, or human immunodeficiency virus, regardless of LDL-C level. After age 75 years, LDL-C–lowering pharmacotherapy can be considered in conjunction with lifestyle interventions to reduce ASCVD risk.
In secondary prevention, a goal of LDL-C <55 mg/dL (1.4 mmol/L) and non–HDL-C <85 mg/dL (2.2 mmol/L) is recommended for those at very high risk of ASCVD events. Although a smaller number of patients with ASCVD not at very high risk have an LDL-C goal of at least <70 mg/dL, the majority of those with a history of ASCVD events will likely qualify for an LDL-C goal of <55 mg/dL.
In patients with persistently elevated TG, statin therapy remains the foundation of pharmacotherapy as an adjunct to lifestyle intervention to reduce ASCVD risk. Treatment for prevention of pancreatitis may also include TG-lowering therapies, especially in individuals with TG levels ≥1000 mg/dL (11.3 mmol/L).

2.1. Definitions

Cardiovascular-kidney-metabolic syndrome: The common characteristics of the cardiovascular-kidney-metabolic (CKM) syndrome include abdominal obesity (high body mass index [BMI] and/or large waist circumference), insulin-resistant glucose metabolism (hyperinsulinemia, impaired fasting glucose, impaired glucose tolerance, type 2 diabetes), dyslipidemia (high serum TG and low serum high-density lipoprotein cholesterol [HDL-C] concentrations), increased blood pressure, and sometimes microalbuminuria, proteinuria, or chronic kidney disease (CKD).

Children: In this guideline, children are defined as age 18 years or younger.

Clinical ASCVD: ASCVD includes history of acute coronary syndromes (ACS), myocardial infarction (MI), stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack (TIA), or peripheral artery disease (PAD). ASCVD at very high risk is defined as ≥2 major ASCVD events (ACS within the past 12 months, history of MI [other than recent ACS], history of ischemic stroke, symptomatic PAD) or with 1 major ASCVD event and ≥2 high-risk features (age ≥65 years, coronary bypass or percutaneous intervention, current smoker, diabetes, history of heart failure [HF], hypertension, LDL-C ≥100 mg/dL [2.6 mmol/L] despite maximally tolerated statin plus ezetimibe).

Dyslipidemias: Dyslipidemias considered in this guideline include elevated blood cholesterol, hypertriglyceridemia, and elevated Lp(a).

Lifestyle management: Lifestyle management encompasses an assessment of each individual's baseline behavioral habits and counseling regarding healthy lifestyle habits. It includes information regarding heart-healthy eating patterns, regular physical activity, avoidance of all nicotine-delivery products, healthy sleep habits, and maintaining a healthy weight. This includes the lifestyle elements of the AHA’s Life’s Essential 8™ in addition to stress management.

Subclinical atherosclerosis: Subclinical atherosclerosis is identified by the presence of atheromatous disease in ≥1 arterial territories before there are any signs, symptoms, or events attributable to clinically manifest atherosclerotic disease in those territories.

Table 4. ASCVD Risk Related to Lp(a) Concentrations^*

Lp(a) Concentration nmol/L (mg/dL)	ASCVD Relative Risk: Increase Compared With Population Median (20 nmol/L, 7 mg/dL)
430 nmol/L (180 mg/dL)	4-fold
350 nmol/L (150 mg/dL)	3-fold
250 nmol/L (100 mg/dL)	2-fold
125 nmol/L (50 mg/dL)	1.4-fold
75–124 nmol/L (30–49 mg/dL)	1.2-fold
<75 nmol/L (<30 mg/dL)	Reference

^*Lp(a) concentrations in this threshold range may be considered for repeat testing.
Data in the table are derived from the UK Biobank Study, are intended as a general guide and may differ in other populations. For example, relative risk of 2-fold has been observed for levels of 200 nmol/L in some populations. Equivalence of levels between nmol/L and mg/ dL is approximate. An Lp(a) level of 50 mg/dL (125 nmol/L, ~80th percentile) is associated with an ~40% relative risk increase in ASCVD compared with 7 mg/dL (20 nmol/L, median in a reference population). An Lp(a) level of 100 mg/dL (≥250 nmol/L, ~95th percentile) approximately doubles the ASCVD risk. An Lp(a) level of 180 mg/dL (≥430 nmol/L, ~99th percentile) increases the ASCVD risk by ~4-fold, similar to the risk of heterozygous familial hypercholesterolemia.
ASCVD indicates atherosclerotic cardiovascular disease; and Lp(a), lipoprotein (a).

Table 6. High-, Moderate-, and Low-Intensity Statin Therapy^*

	High-Intensity	Moderate-Intensity	Low-Intensity
Expected % LDL-C Reduction^†	≥50%	30%–49%	<30%
Preferred Statins	Atorvastatin (40 mg) 80 mg Rosuvastatin 20 mg (40 mg)	Atorvastatin 10 mg (20 mg) Rosuvastatin (5 mg) 10 mg
Other Statins	—	Fluvastatin XL 80 mg Fluvastatin 40 mg BID Lovastatin 40 mg (80 mg) Pitavastatin 1, 2, 4 mg Pravastatin 40 mg (80 mg) Simvastatin 20, 40 mg^‡	Fluvastatin 20, 40 mg Lovastatin 20 mg Pravastatin 10, 20 mg Simvastatin 10 mg

Expected percentage LDL-C reductions with atorvastatin, rosuvastatin, and simvastatin were estimated using the median reduction in LDL-C from the VOYAGER database. Reductions in LDL-C for other statins (fluvastatin, lovastatin, pitavastatin, and pravastatin) were identified according to FDA-approved product labeling in adults with hyperlipidemia, primary hypercholesterolemia, and mixed dyslipidemia.

Boldface type indicates specific statins and doses that were evaluated in placebo-controlled RCTs evaluating ASCVD event lowering, and the Cholesterol Treatment Trialists’ 2010 meta-analysis. These RCTs demonstrated a reduction in major ASCVD events.

Modified with permission from Grundy et al. Copyright © 2018 American Heart Association, Inc. and American College of Cardiology Foundation.

^* Expected percentage reductions are estimates from data across large populations. Individual responses to statin therapy varied in the RCTs and should be expected to vary in clinical practice owing to a high degree of heterogeneity seen with LDL-C–lowering medications.
^† Expected LDL-C lowering with the dosage listed below each intensity.
^‡ Although simvastatin 80 mg was evaluated in RCTs, initiation of simvastatin 80 mg or titration to 80 mg is not recommended by the FDA because of the increased risk of myopathy, including rhabdomyolysis.

BID indicates twice daily; FDA, US Food and Drug Administration; LDL-C, low-density lipoprotein-cholesterol; RCT, randomized controlled trial; and XL, extended release.

Table 7. Pharmacokinetic Properties of Statin Medications

	Absorption		Distribution		Metabolism			Elimination
	Bio-availability (%)	Tmax (h)	Protein Binding (%)	Lipophilicity (log P)	CYP Hepatic Enzyme	Pro-drug	Active Metabolite	Renal Excretion (%)	t1/2 (hr)
Atorvastatin	14	1-2	≥98	Yes, 4.1	3A4	No	Yes	<2	14
Fluvastatin	24	<1	98	Yes, 3.2	2C9 (2C8, 3A4 minor)	No	No	5	3
Lovastatin	<5	2-4	≥95	Yes, 4.3	3A4	Yes	Yes	10	2-3
Pitavastatin	43-51	1	99	Yes, 1.5	2C9 (2C8 minor)	No	No	15	12
Pravastatin	17	1-1.5	50	No, -0.2	None	No	No	20	1.8
Rosuvastatin	20	3-5	88	No, -0.3	2C9	No	Minimal	10	19
Simvastatin	<5	4	95	Yes, 4.7	3A4	Yes	Yes	13	2

Atorvastatin, lovastatin, and simvastatin are P-glycoprotein substrates and may be subject to certain drug-drug interactions.

Modified with permission from Wiggins et al. Copyright © 2016 American Heart Association, Inc.

CYP indicates cytochrome P450; h, hour; Tmax, time until maximum serum concentration achieved; and t1/2, drug half-life.

Table 8. Common Medications That May Interact With Statins

Avoid use with any statin	Gemfibrozil
Can be used with a statin using a risk mitigation strategy^*	Amiodarone Amlodipine Atazanavir plus ritonavir Boceprevir Clarithromycin Cobicistat-containing products Colchicine Cyclosporine Danazol Darunavir plus ritonavir Diltiazem Dronedarone Erythromycin Fenofibrate Fenofibric acid Fluconazole Fosamprenavir (with or without ritonavir) Itraconazole
Can be used with a statin using a risk mitigation strategy^*	Ketoconazole Lomitapide Lopinavir plus ritonavir Nefazodone Nelfinavir Niacin (≥1 g/d) Nirmatrelvir plus ritonavir Posaconazole Ranolazine Rifampin Saquinavir plus ritonavir Telaprevir Telithromycin Tipranavir plus ritonavir Verapamil Voriconazole Warfarin

^* Risk mitigation strategies include a) avoiding use of the coadministered interacting medication, b) using an alternative statin that does not have the drug- drug interaction, and c) limiting the statin dose depending upon the statin and the nature of the drug-drug interaction.

Modified with permission from Wiggins et al. Copyright © 2016 American Heart Association, Inc.

Table 9. Considerations for Referral to a Lipid Specialist^*

Patients with diagnosed or suspected FH
- Patients with homozygous FH
- Patients with heterozygous FH who do not achieve treatment targets on maximally tolerated statin plus nonstatin therapy
- Patients with heterozygous FH with statin-attributed side effects on ≥2 statins, including at the lowest dose or with alternate dosing regimens
Patients with ASCVD or at high risk of ASCVD
- Patients with premature ASCVD (onset age <40 years)
- Patients who do not achieve ≥50% LDL-C reduction and LDL-C (or non–HDL-C) targets on maximally tolerated statin plus nonstatin therapy
- Patients with statin-attributed side effects on ≥2 statins, including at the lowest dose or with alternate dosing regimens
- Patients who have elevated Lp(a) (≥200 nmol/L or ≥75 mg/dL)
- Patients <40 years old with diabetes and dyslipidemia
Patients at high risk for ASCVD or with ASCVD who are on complex medication regimens
- Patients receiving treatment for HIV
- Patients receiving treatment for cancer
- Patients receiving treatments to prevent transplant rejection
Individuals who are considering pregnancy, are pregnant, or are breastfeeding
- Patients with heterozygous FH
- Patients with hypertriglyceridemia (TG ≥400 mg/dL)
- Patients with ASCVD or at high risk of ASCVD requiring LLT
Patients with inherited hyperlipidemias who need genetic testing for diagnosis
Patients with severe/extreme primary hypertriglyceridemia after secondary causes have been ruled out
Patients who may be candidates for treatment with evinacumab, lomitapide, olezarsen, or lipoprotein apheresis

^* Especially if patients are not achieving lipid/lipoprotein goals on recommended therapies.

ASCVD indicates atherosclerotic cardiovascular disease; FH, familial hypercholesterolemia; LDL-C, low-density lipoprotein-cholesterol; LLT, lipid-lowering therapy; LP(a), lipoprotein (a); HDL-C, high-density lipoprotein-cholesterol; HIV, human immunodeficiency virus; and TG, triglycerides.

Table 10. Checklist for Individualized Benefit-Risk Discussion

	Checklist Item	Recommendation
✓	ASCVD risk assessment	• Perform ASCVD risk assessment (Sections 4.2.3.2 through 4.2.3.7). • When indicated, use the PREVENT-ASCVD Calculator^. • Explain risk in absolute and relative terms. • Use decision tools to explain risk (eg, PREVENT-ASCVD Calculator^). • Consider CAC scan or the presence and severity of atherosclerosis seen on a non-ECG–gated chest CT or a carotid ultrasound. • Consider risk enhancers. • Consider reproductive age risk markers.
✓	Emphasize healthy lifestyle habits as the foundation of treatment	• Review lifestyle habits (eg, diet, physical activity, weight or body mass index, and tobacco use). • Endorse a healthy lifestyle and provide relevant advice, materials, or referrals (eg, CardioSmart^†, AHA Life’s Essential 8^‡, NLA Patient Tear Sheets^§, PCNA Heart Healthy Toolbox^\|\|, cardiac rehabilitation, dietitian, smoking cessation program).
✓	Potential net clinical benefit of pharmacotherapy	• Recommend a statin as first-line therapy. • Consider the combination of statin • Consider the combination of statin • Consider the combination of statin • Consider the combination of statin • Consider the combination of statin • Consider the combination of statin • Consider the combination of statin • Consider the combination of statin • Consider the combination of statin • Consider the combination of statin • Consider the combination of statin • Consider the combination of statin • Consider the combination of statin statin. • Discuss potential risk reduction from LLT. • Discuss the potential for adverse effects or drug-drug interactions.
✓	Cost and convenience considerations	• Discuss potential out-of-pocket cost of therapy to the patient (eg, insurance plan coverage, tier level, copayment). • Discuss administration of medicine by daily oral therapy, time of administration, potential drug interactions, subcutaneous injection every 2 weeks versus every 6 months.
✓	Shared decision-making	• Encourage the patient to verbalize what was heard (eg, patient’s personal estimated ASCVD risk, available options, and risks/benefits). • Invite the patient to ask questions, express values and preferences, and state ability to adhere to lifestyle changes and medications. • Refer patients to trustworthy materials to aid in their understanding of issues regarding risk decisions. • Collaborate with the patient to determine therapy and follow-up plan.

^* The PREVENT-ASCVD Online Calculator is available at: https://professional.heart.org/en/guidelines-and-statements/prevent calculator.
^† CardioSmart health information is available at: https://www.cardiosmart.org/topics/healthy-living.
^‡ AHA Life's Essential 8 information is available at: https://www.heart.org/en/healthy-living/healthy-lifestyle/lifes-essential-8.
^§ NLA Patient Tear Sheets information is available at: https://www.lipid.org/practicetools/tools/tearsheets.
^|| PCNA Heart Healthy Toolbox information is available at: https://pcna.net/resource/heart-healthy-toolbox/.

AHA indicates American Heart Association; ASCVD, atherosclerotic cardiovascular disease; CAC, coronary artery calcium; CT, computed tomography; ECG, electrocardiogram; LDL-C, low-density lipoprotein-cholesterol; LLT, lipid-lowering therapy; PCNA, Preventive Cardiology Nurses Association; and NLA, National Lipid Association.

Adapted with permission from Martin et al. Copyright © 2015 American College of Cardiology Foundation.

Table 11. Salient Features of the American Heart Association PREVENT^TM* Equations

The PREVENT equations:

Included a large, contemporary, representative sample of U.S. adults for derivation (N ~3.3 million) and external validation (N ~3.3 million).
Lower limit to begin risk prediction to age 30 years (through 79 years).
Provide sex-specific equations; race/ethnicity is not a variable that added predictive value to the equations and provides estimates adjusted for competing risk of non-CVD death.
Provide a base model for risk prediction that includes commonly available risk factor measures: age, sex, blood pressure, total and HDL-C, diabetes status, tobacco use, kidney function (eGFR), statin use, and antihypertensive medication use (and BMI for heart failure prediction).
Provide optional models with additional inputs, if known/measured, of hemoglobin A1c (to capture glycemic status), urinary albumin/creatinine ratio (for proteinuria and CKD), and zip code (to represent social deprivation index and acknowledge social determinants of cardiovascular risk). These factors are not necessary to generate risk estimates, but they may enhance risk prediction if available.
Predict 10-year and 30-year outcomes.
Predict risk for hard ASCVD^† (relevant for LLT decisions), HF, and total CVD (ASCVD plus HF; relevant for blood pressure-lowering therapy decisions).
Demonstrate similar risk discrimination (C statistics) as the pooled cohort equations for prediction of ASCVD events.
Provide significantly and substantially more accurate risk estimates (improved calibration) for ASCVD than the pooled cohort equations, overall and in all demographic subgroups. In general, risk estimates from PREVENT-ASCVD equations tend to be 40% to 50% lower than 10-year risk estimates from the pooled cohort equations for the same risk factor profile.

^* For the purposes of risk assessment in decision-making for LLT, the PREVENT-ASCVD equations version should be used to predict hard ASCVD outcomes and assist the patient-clinician risk/benefit discussion.
^† Fatal or nonfatal stroke, nonfatal MI, or CHD death. This does not include revascularizations performed without antecedent clinical events, given wide variation in practice patterns.

Adapted with permission from Khan et al. Copyright © 2023 American Heart Association, Inc.

ASCVD indicates atherosclerotic cardiovascular disease; BMI, body mass index; CVD, cardiovascular disease; CHD, coronary heart disease; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HDL-C, high-density lipoprotein-cholesterol; HF, heart failure; LLT, lipid-lowering therapy; and MI, myocardial infarction.

Figure 4. Logic for Defining the Absolute Estimated 10-Year ASCVD Risk for Consideration of LLT at ≥3% in Primary Prevention

The graphs plot the number-needed-to-treat to prevent 1 ASCVD event (NNT-benefit; y-axis) as a function of the observed 10-year ASCVD event rate (x-axis) from primary prevention RCTs of statin therapy. The red curves show the number-needed-to-treat to prevent 1 ASCVD event (NNT-benefit) with initiation of (A) moderate-intensity or (B) high-intensity statin, assuming a 35% RRR with moderate-intensity and 45% RRR with high-intensity statin, as has been observed in meta-regression of statin trials. The horizontal black lines represent the number-needed-to-treat to cause 1 case of incident diabetes (NND) over 10 years with (A) moderate-intensity or (B) high-intensity statin. The risk of incident diabetes is higher for high-intensity than lower-intensity statins. Individuals with baseline normoglycemia rarely develop elevations in glucose sufficient to cause a new diagnosis of diabetes. Individuals who develop statin-attributed diabetes almost universally have documented prediabetes and are already near the threshold for diagnosis of diabetes.

The points where the red curves and the horizontal black lines cross (blue circle; ~3% 10-year event rates for moderate-intensity and ~7% for high-intensity statin) represent the points at which the NNT-benefit and the NND are equal. Therefore, at risk levels higher than indicated by the dashed lines, there is expected net clinical benefit (potential benefit>potential harm) for initiation of LLT in primary prevention. Given that the PREVENT-ASCVD equations accurately predict ASCVD risk, the threshold for consideration of LLT in primary prevention was set at a 10-year PREVENT-ASCVD 10-year risk estimate of ≥3%.

ASCVD indicates atherosclerotic cardiovascular disease; CVD, cardiovascular disease; DM, diabetes; LLT, lipid-lowering therapy; NND, number-needed-to-treat to cause 1 case of incident diabetes in 10 years; NNT-benefit, number-needed-to-treat to prevent 1 ASCVD event; RCT, randomized controlled trial; and RRR, relative risk reduction.

Adapted with permission from Khan et al. Copyright © 2024 American Heart Association, Inc.

Table 12. Crosswalk Between 10-Year Risk ASCVD Estimates From PCE and PREVENT-ASCVD Equations

	Approximate Equivalent Ranges of 10-Year ASCVD Risk Estimates^*
Risk Group	PCE	PREVENT-ASCVD
Low	<5%	<3%
Borderline	5%–<7.5%	3% to <5%
Intermediate	7.5%–<20%	5% to <10%
High	≥20%	≥10%

^* The PREVENT-ASCVD equations generally provide 10-year risk estimates that are 40% to 50% lower than the PCE estimates because the PCE calculator often overestimated the risk for adults.
ASCVD denotes atherosclerotic cardiovascular disease; and PCE, pooled cohort equations.
Adapted from Khan et al.

Table 13. Risk-Enhancers

Risk-Enhancers

History of premature ASCVD in a parent or sibling (onset age <55 y for men, <65 y for women)
Higher risk ancestry (eg, South Asian, Filipino)
High polygenic risk (if measured) (Section 4.2.3.5, “Polygenic Risk Scores”)
Chronic inflammatory diseases (eg, systemic lupus, rheumatoid arthritis, advanced psoriasis, inflammatory arthritis)
Lp(a) ≥125 nmol/L or ≥50 mg/dL
hsCRP ≥2 mg/L on >1 occasion (if measured)
TG persistently ≥175 mg/dL (2 mmol/L) (if nonfasting) and ≥150 mg/dL (1.7 mmol/L) (if fasting)
CKM syndrome
LDL-C persistently ≥160–189 mg/dL (4.1–4.9 mmol/L), non–HDL-C≥190–219 mg/dL or apoB ≥120 mg/dL^*
Reproductive risk markers (premature menopause, preeclampsia, gestational diabetes, gestational hypertension, preterm delivery; Section 4.2.3.4, “Reproductive Risk Marker”)

Note that all available information should be included in risk estimates derived from the PREVENT-ASCVD equations, including albuminuria, HbA1c, and zip code for assessment of neighborhood-level social determinants of health. Given the recent publication of the PREVENT-ASCVD equations, it remains to be demonstrated for most risk-enhancers that risk is incremental to the PREVENT-ASCVD equations.

^* Although LDL-C is not included in the PREVENT-ASCVD equations (total cholesterol and HDL-C are included), it is included here because persistent elevation of LDL-C may be a useful factor to include in risk-benefit discussions about LDL-C–lowering therapy, given that it is the target of that therapy. See Section 4.2.3.4, “Reproductive Risk Marker,” for more detail regarding reproductive risk factors.

ApoB indicates apolipoprotein B; ASCVD, atherosclerotic cardiovascular disease; CKM, cardiovascular-kidney-metabolic; HbA1c, hemoglobin A1c; HDL-C, high-density lipoprotein-cholesterol; hsCRP, high-sensitivity C-reactive protein; LDL-C, low-density lipoprotein-cholesterol; Lp(a), lipoprotein (a); and TG, triglycerides.

Adapted with permission from Grundy et al. Copyright © 2018 American Heart Association, Inc. and American College of Cardiology Foundation.

Table 15. Liposorber® (LA-15 System) FDA-Approved Indications for Lipoprotein Apheresis^*

Patient Group	Criteria for Treatment
Group A	Clinically diagnosed familial hypercholesterolemic homozygotes with LDL-C >500 mg/dL
Group B	Clinically diagnosed familial hypercholesterolemic heterozygotes with LDL-C ≥300 mg/dL
Group C	Clinically diagnosed familial hypercholesterolemic heterozygotes with LDL-C ≥70 mg/dL and either documented coronary artery disease or documented peripheral artery disease
Group D	Clinically diagnosed familial hypercholesterolemic heterozygotes with Lp(a) ≥60 mg/dL (or 130 nmol/L) and either documented coronary artery disease or documented peripheral artery disease

Disclaimer: The device listed here serves only to illustrate examples of these types of FDA-approved devices. This is not intended to be an endorsement of any commercial product, process, service, or enterprise by the AHA or the ACC.

^* As of January 2025: for updated indications for use, please review the website: https://liposorber.com/posts/expanded-indication-for-kanekas-liposorber-la-15-system/ FDA indicates US Food and Drug Administration; LDL-C, low-density lipoprotein-cholesterol; and Lp(a), lipoprotein(a).

FDA indicates US Food and Drug Administration; LDL-C, low-density lipoprotein-cholesterol; and Lp(a), lipoprotein(a).

Table 19. Lipid-Lowering Agents in Childhood and Adolescents (eg, <Age 18 Years)

Class	Medication	FDA approved dosing for use in childhood	FDA indicated age	Expected LDL-C reduction at maximum pediatric dose	Potential adverse effects
Statins	Atorvastatin	5 mg, 10 mg, 20 mg, 40 mg, 8 mg PO/d	≥10 y	≥50%	Myalgias (rare), abdominal pain (rare), accelerated risk of diabetes type 2 (unknown, reported in adults), hepatotoxicity (very rare), HMG-CoA antibody myopathy (very rare) rhabdomyolysis (extremely rare)
Statins	Pitavastatin	1 mg, 2 mg, 4 mg PO/d	≥8 y	30–49%	Myalgias (rare), abdominal pain (rare), accelerated risk of diabetes type 2 (unknown, reported in adults), hepatotoxicity (very rare), HMG-CoA antibody myopathy (very rare) rhabdomyolysis (extremely rare)
Statins	Pravastatin	10 mg, 20 mg, 40 mg PO/d	≥8 y	30–49%	Myalgias (rare), abdominal pain (rare), accelerated risk of diabetes type 2 (unknown, reported in adults), hepatotoxicity (very rare), HMG-CoA antibody myopathy (very rare) rhabdomyolysis (extremely rare)
Statins	Simvastatin	5 mg, 10 mg, 20 mg, 40 mg^* PO/d	≥10 y	30–49%	Myalgias (rare), abdominal pain (rare), accelerated risk of diabetes type 2 (unknown, reported in adults), hepatotoxicity (very rare), HMG-CoA antibody myopathy (very rare) rhabdomyolysis (extremely rare)
Statins	Rosuvastatin	5 mg, 10 mg, 20 mg PO/d	≥8 y for 5 and 10 mg doses and >10 y for 20 mg dose	≥50%	Myalgias (rare), abdominal pain (rare), accelerated risk of diabetes type 2 (unknown, reported in adults), hepatotoxicity (very rare), HMG-CoA antibody myopathy (very rare) rhabdomyolysis (extremely rare)
Cholesterol absorption inhibitors	Ezetimibe	10 mg PO/d	≥10 y	13–20%	Myalgias, muscle weakness, fatigue, diarrhea (all very rare)
Cholesterol absorption inhibitors	Bile acid binding resin	Colesevelam: 3.75 g PO/d as 1 packet or six 625 mg tablets divided twice daily	≥10 y	15%	Significant drug interactions exist. Contraindicated if TG are elevated (will raise TG). Abdominal pain, constipation (rare), pancreatitis (very rare)
PCSK9 monoclonal antibodies	Evolocumab	140 mg SQ every 2 wk or 420 mg SQ every 2 wk^†	≥10 y	38% (HeFH) 14% (HoFH)	Hypersensitivity (rare), nasopharyngitis (common), headache, sore throat (common)
PCSK9 monoclonal antibodies	Alirocumab	Pediatric dosing by weight in 2- or 4-wk intervals SQ	≥8 y	34–44% (HeFH) 13% (HoFH)	Nasopharyngitis (common), tonsilitis (common), headache (common), injection site reaction (common). Attention and memory problems, syncope were rarely reported.
Other cholesterol-lowering medications	Evinacumab	15 mg/kg IV q 4 wk	≥5 y old HoFH only	48% (HoFH)	Fatigue, pyrexia, headache, oropharyngeal pain, nasopharyngitis, abdominal pain
Supplements	Psyllium fiber	10 g PO/d		6–24%	GI effects, although these tend to resolve with regular use
Supplements	Plant Stanol/Sterol	2 g PO/d (available as capsules or as food additives)		6–12%	Diarrhea, steatorrhea

^* The 80 mg dose of simvastatin should not be used due to myopathy risk.
^† The 420 mg dose of evolocumab is no longer manufactured for administration.

Dosing information and contraindications from FDA-approved labeling available at: http://dailymed.nlm.nih.gov/dailymed/index.cfm

HeFH, heterozygous familial hypercholesterolemia; HoFH, homozygous familial hypercholesterolemia; IV, intravenous; PO, per os; and SQ, subcutaneous.

Table 20. Lipid-Lowering Therapies During Pregnancy and Lactation

	Pregnancy	Lactation
Statins	Should be discontinued in most pregnancies Can be considered in high-risk individuals (ASCVD or FH)	Avoid use
Ezetimibe	Avoid use due to insufficient data regarding risk to fetus	Avoid use
Bile acid sequestrants	Safe to use. No evidence of risk in humans due to lack of systemic absorption. Known to interfere with absorption of fat-soluble vitamins High rate of gastrointestinal side effects	Not excreted in human milk Caution if used — associated with malabsorption of fat-soluble vitamins (A, D, E, and K) Prenatal vitamins may not be sufficient.
Niacin	Avoid use due to insufficient data regarding risk to fetus or clinical utility for the mother	Avoid use
Fibric acid derivatives	Can be considered (after the first trimester) for severe hypertriglyceridemia only if the potential benefit justifies the potential risk to the fetus	Avoid use during lactation. If taken during pregnancy, lactation can be resumed 5 days after last dose of fibric acid derivatives.
Omega-3 fatty acids	Can be considered for severe hypertriglyceridemia	Known to be excreted in human milk. Effects on infants are unknown. Caution if used during lactation
Bempedoic acid	Avoid use due to insufficient data regarding risk to fetus	Avoid use
PCSK9 mAb	Avoid use due to insufficient data regarding risk to fetus	Avoid use
Inclisiran	Avoid use due to insufficient data regarding risk to fetus	Avoid use
Evinacumab	Avoid use due to insufficient data regarding risk to fetus	Avoid use
Lomitapide	Avoid use due to risk of embryo-fetal toxicity	Avoid use

ASCVD indicates atherosclerotic cardiovascular disease; FH, familial hypercholesterolemia; mAb, monoclonal antibodies; and PCSK9 proprotein convertase subtilisin/kexin type 9.
Adapted with permission from Agarwala et al. Copyright © 2024 Elsevier. Adapted with permission from Jacobson et al. Copyright © 2015 Elsevier.

Table 22. Antiretroviral Therapy and Statin Drug Interactions - Protease Inhibitors

Statin	Antiretroviral Drug	Recommendations
Atorvastatin	Atazanavir Atazanavir/ritonavir	Titrate atorvastatin dose carefully and administer the lowest effective dose while monitoring for toxicities.
Atorvastatin	Atazanavir/cobicistat	Do not coadminister.
Atorvastatin	Darunavir/cobicistat Darunavir/ritonavir	Titrate atorvastatin dose carefully and administer the lowest effective dose while monitoring for toxicities. Do not exceed atorvastatin 20 mg daily.
Atorvastatin	Lopinavir/ritonavir	Titrate atorvastatin dose carefully and administer the lowest effective dose while monitoring for toxicities. Do not exceed atorvastatin 20 mg daily.
Atorvastatin	Tipranavir/ritonavir	Do not coadminister.
Lovastatin	All protease inhibitors	Contraindicated.
Pitavastatin	All protease inhibitors	No dose adjustment needed.
Pravastatin	Atazanavir/ritonavir Atazanavir/cobicistat	Titrate pravastatin dose carefully while monitoring for pravastatin-related adverse events.
Pravastatin	Darunavir/cobicistat Darunavir/ritonavir	Titrate pravastatin dose carefully while monitoring for pravastatin-related adverse events.
Pravastatin	Lopinavir/ritonavir	No dose adjustment needed.
Rosuvastatin	Atazanavir/ritonavir	Titrate rosuvastatin dose carefully and administer lowest effective dose while monitoring for rosuvastatin-related adverse events.
Rosuvastatin	Atazanavir/cobicistat	Do not exceed rosuvastatin 10 mg daily.
Rosuvastatin	Darunavir/cobicistat	Titrate rosuvastatin dose carefully and administer lowest effective dose while monitoring for rosuvastatin-related adverse events. Do not exceed rosuvastatin 20 mg daily.
Rosuvastatin	Darunavir/ritonavir	Titrate rosuvastatin dose carefully and administer the lowest effective dose while monitoring for rosuvastatin-related adverse events.
Rosuvastatin	Lopinavir/ritonavir	Titrate rosuvastatin dose carefully and administer the lowest effective dose. Do not exceed rosuvastatin 10 mg daily.
Rosuvastatin	Tipranavir/ritonavir	No dose adjustment needed.
Simvastatin	All protease inhibitors	Contraindicated.

Table 22. Antiretroviral Therapy and Statin Drug Interactions - NNRTIs

Statin	Antiretroviral Drug	Recommendations
Atorvastatin	Doravirine Rilpivirine	No dose adjustment needed.
Atorvastatin	Efavirenz Etravirine	Adjust atorvastatin dose according to lipid response, but do not exceed the maximum recommended dose.
Atorvastatin	Nevirapine	Adjust atorvastatin dose according to lipid response, but do not exceed the maximum recommended dose.
Fluvastatin	Doravirine Rilpivirine Nevirapine	No dose adjustment needed.
Fluvastatin	Efavirenz Etravirine	Dose adjustments for fluvastatin may be necessary. Monitor for fluvastatin toxicity.
Lovastatin Simvastatin	Doravirine Rilpivirine	No dose adjustment needed.
Lovastatin Simvastatin	Efavirenz	Adjust simvastatin dose according to lipid response, but do not exceed the maximum recommended dose.
Lovastatin Simvastatin	Etravirine Nevirapine	Adjust lovastatin or simvastatin dose according to lipid response, but do not exceed the maximum recommended dose.
Pitavastatin	All NNRTIs	No dose adjustment needed.
Pravastatin	Doravirine Rilpivirine Nevirapine	No dose adjustment needed.
Pravastatin	Efavirenz Etravirine
Rosuvastatin	All NNRTIs	No dose adjustment needed.

NNRTI indicates non-nucleoside reverse transcriptase inhibitor; and NRTI, nucleoside reverse transcriptase inhibitor.
Adapted from and modified with permissions from Sarkar et al. Copyright © 2000–2025 MDText.com, Inc.

Table 22. Antiretroviral Therapy and Statin Drug Interactions - NRTIs

Statin	Antiretroviral Drug	Recommendations
All statins	All NRTIs	No dose adjustment needed.

Table 22. Antiretroviral Therapy and Statin Drug Interactions - Integrase Strand Transfer Inhibitors

Statin	Antiretroviral Drug	Recommendations
Atorvastatin	Bictegravir Dolutegravir Raltegravir	No dose adjustment needed.
Atorvastatin	Elvitegravir/cobicistat	Titrate statin dose carefully and administer the lowest effective dose while monitoring adverse events. Do not exceed atorvastatin 20 mg daily.
Lovastatin	Bictegravir Dolutegravir Raltegravir	No dose adjustment needed.
Lovastatin	Elvitegravir/cobicistat	Contraindicated.
Pitavastatin Pravastatin	Bictegravir Dolutegravir Raltegravir	No dose adjustment needed.
Pitavastatin Pravastatin	Elvitegravir/cobicistat	No data available for dose recommendation.
Rosuvastatin	Bictegravir Dolutegravir Raltegravir	No dose adjustment needed.
Rosuvastatin	Elvitegravir/cobicistat	Titrate statin dose carefully and use the lowest effective dose while monitoring for adverse events.
Simvastatin	Bictegravir Dolutegravir Raltegravir	No dose adjustment needed.
Simvastatin	Elvitegravir/cobicistat	Contraindicated.

Table 23. Physiological and Secondary Causes of Hypertriglyceridemia

Categories	Conditions and Medications Contributing to Hypertriglyceridemia
Diseases	Poorly controlled diabetes Chronic kidney disease, nephrotic syndrome Lipodystrophy Uncontrolled hypothyroidism Cushing syndrome Glycogen storage disease, acute hepatitis Rheumatoid arthritis Psoriasis Systemic lupus erythematosus Multiple myeloma Sepsis (repeat measurement is recommended if lipids were measured during an episode of sepsis)
Diet/Lifestyle	History of alcohol abuse or alcohol excess Diets high in saturated fat, sugar, or high-glycemic-index foods Sedentary lifestyle Total parenteral nutrition with lipid emulsions
Drugs^* (Medications)	Anesthesia: Propofol Cardiology: Beta-adrenergic–blocking agents Thiazide and loop diuretic agents Bile acid sequestrants (cholestyramine, colestipol, colesevelam) Endocrine: Glucocorticosteroids Anabolic steroids Oral estrogens Raloxifene Clomiphene citrate Estradiol Ethinyl estradiol Conjugated estrogens Tamoxifen Dermatology: Isotretinoin Infectious Disease: HIV protease inhibitors Oncology: Tamoxifen L-asparaginase Bexarotene Cyclophosphamide Psychiatry: Atypical antipsychotic agents (eg, olanzapine, mirtazapine, clozapine) Immunosuppressive agents: Tacrolimus Sirolimus Cyclosporine Interferons
Disorders of metabolism	Overweight and obesity Metabolic syndrome/insulin resistance Weight gain after weight loss
Physiological	Pregnancy (especially during the third trimester, when pregnancyassociated TG elevation is peaking)

^* Caveats: TG-raising medications require careful monitoring; minimizing other conditions that raise TG; and, when clinically appropriate, using alternatives.
TG indicates triglycerides.
Adapted from Virani et al.

Table 25. Safety Considerations for LDL-C–Lowering Medications

Medication Class	Common Side Effects	Contraindications^*	Comments
HMG-CoA reductase inhibitors (statins)	Myalgia (normal CK level) is common and dose-related	Acute liver failure; decompensated cirrhosis; lactation; severe underlying neuromuscular diseases (eg, dermatomyositis, muscular dystrophy)	See Section 4.2.11, “Management of Statin-Attributed Muscle Symptoms” Myositis/myopathy (CK >ULN) with concerning symptoms or objective weakness is rare; rhabdomyolysis (CK >10 times ULN with renal injury) is rare; immune-mediated necrotizing myopathy (with HMGCR antibodies) is very rare Transaminase elevations (>3 times ULN) are rare Postmarketing reports of cognitive impairment (eg, memory loss, forgetfulness) are rare, generally nonserious, reversible upon statin discontinuation, and not observed in prospective clinical trials See Section 4.2.8.4, “Management of Dyslipidemia in Persons Planning Pregnancy, During Pregnancy, or While Lactating”, pregnancy is not a contraindication, but statins should be avoided while lactating^†
Cholesterol absorption inhibitor (ezetimibe)	Typically well tolerated	Prior hypersensitivity to ezetimibe	Not recommended in patients with moderate or severe hepatic impairment Persistent elevations in hepatic transaminase (>3 times ULN) can occur when added to a statin; monitor hepatic transaminase levels before and after initiating statin with ezetimibe combination therapy
PCSK9 inhibitor: monoclonal antibodies (alirocumab, evolocumab)	Injection site reactions	Prior hypersensitivity to the PCSK9 monoclonal antibody	Hypersensitivity reactions (including angioedema) are rare Latex is in some evolocumab single-dose prefilled syringe covers; alirocumab products do not contain latex
ATP citrate lyase inhibitor (bempedoic acid)	Typically well tolerated	Prior serious hypersensitivity reaction to bempedoic acid or any of the excipients	Elevated BUN, creatinine, and uric acid have been reported (monitoring serum urate level necessary in patients with preexisting and untreated hyperuricemia)
PCSK9 inhibitor: small-interfering RNA (inclisiran)	Injection site reactions	Prior serious hypersensitivity to inclisiran or any of the excipients	Hypersensitivity reactions (including angioedema) are rare
Bile acid sequestrants	Abdominal pain, bloating, dyspepsia, nausea, and constipation are common	TG >500 mg/dL (colesevelam); history of hypertriglyceridemia-induced pancreatitis; bowel obstruction	Poor tolerability due to side effects and potential drug-drug interactions limits use; may decrease absorption of fat-soluble vitamins and folic acid; generally considered the safest medication in pregnancy
Microsomal triglyceride transfer protein inhibitor (lomitapide)	Gastrointestinal effects (ie, diarrhea, nausea, vomiting, dyspepsia, abdominal pain) are common; elevated hepatic transaminases; increased hepatic fat; embryo-fetal toxicity	Pregnancy, concomitant use with a CPY3A4 inhibitor, moderate or severe hepatic impairment or active liver disease including unexplained persistent abnormal liver function tests	Use is restricted to patients with HoFH Available only through a restricted REMS program that ensures safe use requiring regular monitoring of liver function and other health parameters
ANGPTL3 inhibitor (evinacumab)	Serious hypersensitivity reactions; embryo-fetal toxicity	History of serious hypersensitivity reactions to evinacumab-dgnb or to any of its excipients	Use is restricted to patients with HoFH Infusion rate can be slowed, interrupted, or discontinued if signs of adverse reactions, including infusion or hypersensitivity reactions are present during administration

^* Contraindications from FDA-approved labeling (available at: http://dailymed.nlm.nih. gov/dailymed/index.cfm)
^† The Food and Drug Administration has removed pregnancy as a contraindication to statin therapy.
ANGPTL3 indicates angiopoietin-like protein 3; ATP, adenosine triphosphate; CK, creatine kinase; HMG-CoA, 3-hydroxy-3-methylglutaryl- coenzyme; HoFH, homozygous familial hyperlipidemia; mRNA, messenger ribonucleic acid; PCSK9, proprotein convertase subtilisin/kexin type 9; REMS, Risk Evaluation and Mitigation Strategy; RNA, ribonucleic acid; and ULN, upper limit of normal.

Table 26. Safety Considerations for Triglyceride-Lowering Medications

Medication Class	Common Side Effects	Contraindications^*	Comments
Fibrates (fenofibrate, fenofibric acid, gemfibrozil)	Myalgia; persistently elevated hepatic transaminases	Severe renal dysfunction; active liver disease; gallbladder disease; during lactation; history of hypersensitivity to the fibrate product	Fenofibrate and fenofibric acid can reversibly elevate serum creatinine When given in combination with statin therapy can increase risk of muscle toxicity; gemfibrozil should not be used in combination with a statin; fenofibrate or fenofibric acid can be used in combination with statin with monitoring
Omega-3 fatty acids (icosapent ethyl, omega-3-acid ethyl esters)	Eructation, dyspepsia, and taste perversion	History of hypersensitivity to the omega-3 fatty acid product	Side effects less with prescription omega-3 fatty acids compared to nonprescription fish oil supplements New onset atrial fibrillation/flutter reported Must monitor hepatic transaminases in patients with hepatic impairment DHA-containing products (omega-3 acid ethyl esters) can raise LDL-C, but not apoB Derived from fish and purified; use with caution in patients with known hypersensitivity to fish and/or shellfish Possible increased bleeding when used in combination with an antithrombotic agent
Niacin	Facial flushing, gastrointestinal symptoms (diarrhea, nausea, vomiting) are common; persistent hepatic transaminase and glucose elevations	Active liver disease (including unexplained persistent elevated hepatic transaminases), active peptic ulcer disease, arterial bleeding, known hypersensitivity to product components	Monitoring liver enzymes before and during treatment is necessary May cause and/or exacerbate insulin resistance Infrequently used owing to poor tolerability and lack of proven cardiovascular benefits; tolerability improved with long-acting products and by optimizing administration (slow titration, administering with food, predosing with aspirin or an NSAID) Serious muscle toxicity possible with statin use
ApoC-III inhibitor: ASO-directed therapy (olezarsen)	Injection site reactions	Prior serious hypersensitivity to olezarsen or any of the excipients	Use is restricted to patients with FCS Decreased platelet count is possible but not common

^* Contraindications from FDA-approved labeling (available at: http://dailymed.nlm.nih.gov/dailymed/index.cfm).
ApoC-III indicates apolipoprotein C-III; ASO, antisense oligonucleotide; DHA, docosahexanoic acid; FCS, familial chylomicronemia syndrome; and NSAID, nonsteroidal anti-inflammatory drug.

Table 27. Clinical Recommendations on Management of DDI With Statins and Cardiovascular Medications

Interacting Drug	Statin	Clinical Recommendation for Management
Amiodarone	Lovastatin	Limit dose of lovastatin to 40 mg daily
Amiodarone	Simvastatin	Limit dose of simvastatin to 20 mg daily
Amlodipine	Lovastatin	Limit dose of lovastatin to 20 mg daily
Amlodipine	Simvastatin	Limit dose of simvastatin to 20 mg daily
Bempedoic acid	Pravastatin	Limit dose of pravastatin to 40 mg daily
Bempedoic acid	Simvastatin	Limit dose of simvastatin to 20 mg daily
Colchicine	Atorvastatin	Closer monitoring for muscle-related toxicity is recommended when used in combination
Colchicine	Atorvastatin	Closer monitoring for muscle-related toxicity is recommended when used in combination
Colchicine	Fluvastatin	Closer monitoring for muscle-related toxicity is recommended when used in combination
Colchicine	Lovastatin	Closer monitoring for muscle-related toxicity is recommended when used in combination
Colchicine	Pitavastatin	Closer monitoring for muscle-related toxicity is recommended when used in combination
Colchicine	Pravastatin	Closer monitoring for muscle-related toxicity is recommended when used in combination
Colchicine	Rosuvastatin	Closer monitoring for muscle-related toxicity is recommended when used in combination
Colchicine	Simvastatin	Closer monitoring for muscle-related toxicity is recommended when used in combination
Conivaptan	Lovastatin	Avoid combination
Conivaptan	Simvastatin	Avoid combination
Diltiazem	Lovastatin	Limit dose of lovastatin to 20 mg daily
Diltiazem	Simvastatin	Limit dose of simvastatin to 10 mg daily
Dronedarone	Lovastatin	Limit dose of lovastatin to 10 mg daily
Dronedarone	Simvastatin	Limit dose of simvastatin to 10 mg daily
Gemfibrozil	Atorvastatin	Avoid combination
Gemfibrozil	Lovastatin	Avoid combination
Gemfibrozil	Pitavastatin	Avoid combination
Gemfibrozil	Pravastatin	Avoid combination
Gemfibrozil	Rosuvastatin	Avoid combination
Gemfibrozil	Simvastatin	Avoid combination
Lomitapide	Lovastatin	Reduce dose of lovastatin by 50%
Lomitapide	Simvastatin	Reduce dose of simvastatin by 50% and limit dose to 20 mg daily
Ranolazine	Lovastatin	Combination is acceptable to use if clinically indicated and an alternative non-CYP3A4 statin cannot be used. However, doses of lovastatin or simvastatin should not exceed 20 mg daily.
Ranolazine	Simvastatin	Combination is acceptable to use if clinically indicated and an alternative non-CYP3A4 statin cannot be used. However, doses of lovastatin or simvastatin should not exceed 20 mg daily.
Ticagrelor	Atorvastatin	Combination is acceptable without dose limitations
Ticagrelor	Lovastatin	Limit dose of lovastatin to 40 mg daily
Ticagrelor	Simvastatin	Limit dose of simvastatin to 40 mg daily
Verapamil	Lovastatin	Limit dose of lovastatin to 20 mg daily
Verapamil	Simvastatin	Limit dose of simvastatin to 10 mg daily

DDI indicates drug-drug interaction.
Modified with permission from Kellick et al. Copyright © 2014 Elsevier. Modified with permission from Wiggins et al. Copyright © 2016 American Heart Association, Inc. See additional references for prescribing information for each statin.

Class of Recommendations and Level of Evidence

Class (Strength) of Recommendation
CLASS 1 (STRONG) Benefit >>> Risk
Suggested phrases for writing recommendations: Is recommended Is indicated/useful/effective/beneficial Should be performed/administered/other Comparative-Effectiveness Phrases^†: Treatment/strategy A is recommended/indicated in preference to treatment B Treatment A should be chosen over treatment B
CLASS 2a (MODERATE) Benefit >> Risk
Suggested phrases for writing recommendations: Is reasonable Can be useful/effective/beneficial Comparative-Effectiveness Phrases^†: Treatment/strategy A is probably recommended/indicated in preference to treatment B It is reasonable to choose treatment A over treatment B
CLASS 2b (WEAK) Benefit ≥ Risk
Suggested phrases for writing recommendations: May/might be reasonable May/might be considered Usefulness/effectiveness is unknown/unclear/uncertain or not well established
CLASS 3: No Benefit (MODERATE) (Generally, LOE A or B use only) Benefit = Risk
Suggested phrases for writing recommendations: Is not recommended Is not indicated/useful/effective/beneficial Should not be performed/administered/other
CLASS 3: Harm (STRONG) Risk > Benefit
Suggested phrases for writing recommendations: Potentially harmful Causes harm Associated with excess morbidity/mortality Should not be performed/administered/other

Level (Quality) of Evidence^‡
LEVEL A
High-quality evidence^‡ from more than 1 RCT Meta-analyses of high-quality RCTs One or more RCTs corroborated by high-quality registry studies
LEVEL B-R (Randomized)
Moderate-quality evidence^‡ from 1 or more RCTs Meta-analyses of moderate-quality RCTs
LEVEL B-NR (Nonrandomized)
Moderate-quality evidence^‡ from 1 or more well-designed, well-executed nonrandomized studies, observational studies, or registry studies Meta-analyses of such studies
LEVEL C-LD (Limited Data)
Randomized or nonrandomized observational or registry studies with limitations of design or execution Meta-analyses of such studies Physiological or mechanistic studies in human subjects
LEVEL C-EO (Expert Opinion)
Consensus of expert opinion based on clinical experience

COR and LOE are determined independently (any COR may be paired with any LOE).

A recommendation with LOE C does not imply that the recommendation is weak. Many important clinical questions addressed in guidelines do not lend themselves to clinical trials. Although RCTs are unavailable, there may be a very clear clinical consensus that a particular test or therapy is useful or effective.

* The outcome or result of the intervention should be specified (an improved clinical outcome or increased diagnostic accuracy or incremental prognostic information).
^† For comparative-effectiveness recommendations (COR I and IIa; LOE A and B only), studies that support the use of comparator verbs should involve direct comparisons of the treatments or strategies being evaluated.
^‡ The method of assessing quality is evolving, including the application of standardized, widely used, and preferably validated evidence grading tools; and for systematic reviews, the incorporation of an Evidence Review Committee.

COR indicates Class of Recommendation; EO, expert opinion; LD, limited data; LOE, Level of Evidence; NR, nonrandomized; R, randomized; RCT, randomized controlled trial.

Abbreviations

ABI: ankle-brachial index

ACS: acute coronary syndrome

aHR: adjusted hazard ratio

AOR: adjusted odds ratio

apoB: apolipoprotein B

ARR: absolute risk reduction

ASCVD: atherosclerotic cardiovascular disease

ATP: adenosine triphosphate

AU: Agatston units

AUC: area under the curve

BMI: body mass index

CAC: coronary artery calcium

CAD: coronary artery disease

CCTA: cardiac computed tomography angiography

CHD: coronary heart disease

CI: confidence interval

CID: chronic inflammatory diseases

CK: creatine kinase

CKD: chronic kidney disease

CKM: cardiovascular-kidney-metabolic

CT: computed tomography

CTA: computed tomography angiography

CVD: cardiovascular disease

CVOT: cardiovascular outcome trial

CYP3A4: cytochrome P450 3A4

DASH: Dietary Approaches to Stop Hypertension

DDI: drug-drug interactions

DHA: docosahexaenoic acid

eGFR: estimated glomerular filtration rate

EPA: eicosapentaenoic acid

FCS: familial chylomicronemia syndrome

FDA: Food and Drug Administration

FH: familial hypercholesterolemia

HDL-C: high-density lipoprotein-cholesterol

HeFH: heterozygous familial hypercholesterolemia

HF: heart failure

HFrEF: heart failure with reduced ejection fraction

HIV: human immunodeficiency virus

HMG-CoA: 3-hydroxy-3-methylglutaryl- coenzyme

HoFH: homozygous familial hypercholesterolemia

HR: hazard ratio

hsCRP: high-sensitivity C-reactive protein

IPE: icosapent ethyl

LDL: low density lipoprotein

LDL-C: low density lipoprotein-cholesterol

LLT: lipid-lowering therapy

Lp(a): lipoprotein(a)

LpL: lipoprotein lipase

mAbs: monoclonal antibodies

MACE: major adverse cardiovascular event

MASLD: metabolic dysfunction-associated steatotic liver disease

MCS: multifactorial chylomicronemia syndrome

MI: myocardial infarction

NIH: National Institutes of Health

PAD: peripheral artery disease

PCSK9i: proprotein convertase subtilisin/kexin type 9 inhibitor

PLHIV: persons living with HIV

PREVENT: Predicting Risk of cardiovascular disease EVENTs

PRS: polygenic risk scoring

QOL: quality of life

RCT: randomized controlled trial

RDN: registered dietitian nutritionist

RNA: Ribonucleic acid

RRR: relative risk reduction

SAMS: statin-associated muscle symptoms

TC: total cholesterol

TG: triglycerides

VLDL: very low density lipoprotein

Source Citation

Blumenthal, RS, Morris, PB, Gaudino, M, Johnson, HM, Anderson, TS, Bittner, VA, Blankstein, R, Brewer, LC, Cho, L, de Ferranti, SD, Gianos, E, Gluckman, TJ, Gradney, K, Isiadinso, I, Lloyd-Jones, DM, Marrs, JC, Martin, SS, McLain, KH, Mehta, LS, Mora, S, Mulugeta, WM, Natarajan, P, Navar, AM, Orringer, CE, Polonsky, TS, Reynolds, HR, Saseen, JJ, Shapiro, MD, Soffer, DE, Tynes, SA, Villavaso, CD, Virani, SS, Wilkins, JT. 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. [published online ahead of print March 13, 2026]. J Am Coll Cardiol. doi: 10.1016/j.jacc.2025.11.016.

Copublished in Circulation. doi: 10.1161/CIR.0000000000001423

Disclaimer

This resource is for informational purposes only, intended as a quick-reference tool based on the cited source guideline(s), and should not be used as a substitute for the independent professional judgment of healthcare providers. Practice guidelines are unable to account for every individual variation among patients or take the place of clinician judgment, and the ultimate decision concerning the propriety of any course of conduct must be made by healthcare providers after consideration of each individual patient situation. Guideline Central does not endorse any specific guideline(s) or guideline recommendations and has not independently verified the accuracy hereof. Any use of this resource or any other Guideline Central resources is strictly voluntary.

	Acceptable, mg/dL	Borderline, mg/dL	Abnormal, mg/dL
TC	<170 mg/dL	170–199 mg/dL	≥200 mg/dL
TG: 0–9 y	<75 mg/dL	75–99 mg/dL	≥100 mg/dL
TG: 10–19 y	<90 mg/dL	90–129 mg/dL	≥130 mg/dL
HDL-C	>45 mg/dL	40–45 mg/dL	<40 mg/dL
LDL-C	<110 mg/dL	110–129 mg/dL	≥130 mg/dL
Non–HDL-C	<120 mg/dL	120–144 mg/dL	≥145 mg/dL

Management of Dyslipidemia

Introduction

Top Take-Home Messages

Definitions and Classifications

2.1. Definitions

Evaluation and Diagnosis

3.1. Screening in Children and Adults

3.2. Measurement of TC, LDL-C, HDL-C, Triglycerides, and Non–HDL-C

3.3. Measurement of Apolipoprotein B

3.4. Measurement of Lipoprotein (a)

Table 4. ASCVD Risk Related to Lp(a) Concentrations*

3.5. Monitoring and Follow-Up

Figure 1. Lipoprotein Goals for ASCVD Risk Reduction

Management

4.1. Lifestyle Management

4.1.1. Primordial Prevention of Dyslipidemia: Childhood Through Adulthood

4.1.2. Dietary Approaches in Dyslipidemia

4.1.2.1. Dietary Management of LDL-C Disorders

4.1.2.2. Lifestyle Management of Hypertriglyceridemia

4.1.3. Attainment and Maintenance of Healthy Weight in People With Dyslipidemia

4.1.4. Physical Activity

4.1.5. Dietary Supplements

4.1.6. When to Refer to a Registered Dietitian Nutritionist

Figure 2. Health Behavior Interventions in Patients With Hypertriglyceridemia

4.2. Medical Management

4.2.1. Pharmacological Therapy

Table 5. Characteristics of Common Lipid-Lowering Medications to Treat Dyslipidemia* (cont'd)LDL-C-Lowering Medications

Table 5. Characteristics of Common Lipid-Lowering Medications to Treat Dyslipidemia* LDL-C-Lowering Medications (cont'd) LDL-C-Lowering Medications Approved only in HoFH

Table 5. Characteristics of Common Lipid-Lowering Medications to Treat Dyslipidemia* (cont'd)Triglyceride-Lowering Medications

Table 5. Characteristics of Common Lipid-Lowering Medications to Treat Dyslipidemia* (cont'd)Triglyceride-Lowering Medications (cont'd)

4.2.1.1. Statins

Table 6. High-, Moderate-, and Low-Intensity Statin Therapy*

Table 7. Pharmacokinetic Properties of Statin Medications

Table 8. Common Medications That May Interact With Statins

4.2.2. Referring to a Clinical Lipid Specialist

Table 9. Considerations for Referral to a Lipid Specialist*

4.2.3. Primary Prevention in Adults

4.2.3.1. Role of the Individualized Benefit-Risk Discussion

Table 10. Checklist for Individualized Benefit-Risk Discussion

4.2.3.2. PREVENT-ASCVD Equations

Table 11. Salient Features of the American Heart Association PREVENTTM* Equations

Figure 3. Rationale for New 10-Year Risk Thresholds in Lipid-Lowering Therapy Using PREVENT-ASCVD

Figure 4. Logic for Defining the Absolute Estimated 10-Year ASCVD Risk for Consideration of LLT at ≥3% in Primary Prevention

Figure 5. CPR Framework for Risk Evaluation

Table 12. Crosswalk Between 10-Year Risk ASCVD Estimates From PCE and PREVENT-ASCVD Equations

4.2.3.3. Risk Enhancers

Table 13. Risk-Enhancers

4.2.3.4. Reproductive Risk Markers

Table 14. Reproductive Risk Markers Associated With ASCVD Events

4.2.3.5. Polygenic Risk Scores

4.2.3.6. Selective Imaging of Subclinical Atherosclerosis (Men ≥40 or Women ≥45 Years)

4.2.3.7. Primary Prevention in Adults 30 to 79 Years With LDL-C Levels 70 to 189 mg/dL (1.8–4.9 mmol/L)

Low (<3%) Estimated 10-Year ASCVD Risk

Borderline (3% to <5%) and Intermediate (5% to <10%) 10-Year ASCVD Risk

High (≥10%) 10-Year Estimated ASCVD Risk

Special Considerations in Primary Prevention

Figure 6. Primary Prevention in Adults 30 to 79 Years Without ASCVD

4.2.4. Severe Hypercholesterolemia (LDL-C ≥190 mg/dL [4.9 mmol/L])

4.2.4.1. Role of Risk Assessment in Heterozygous Familial Hypercholesterolemia (HeFH)

4.2.4.2. Genetic Testing for Familial Hypercholesterolemia

4.2.4.3. Severe Hypercholesterolemia With LDL-C ≥190 mg/dL (4.9 mmol/L)*

Severe Hypercholesterolemia in Primary Prevention (Without HeFH, Subclinical Atherosclerosis, and Additional ASCVD Risk Factors)

Severe Hypercholesterolemia With HeFH, Subclinical Atherosclerosis, or With Additional Risk Factors

Severe Hypercholesterolemia With Clinical ASCVD

Inclisiran in Severe Hypercholesterolemia

Table 15. Liposorber® (LA-15 System) FDA-Approved Indications for Lipoprotein Apheresis*

Table 16. Physiological and Secondary Causes of Hypercholesterolemia Due to LDL-C

Figure 7. Evaluation and Management of Severe Hypercholesterolemia

Figure 8. Evaluation and Management of HoFH

4.2.4.4. Severe Hypercholesterolemia With Clinical or Genetic Confirmation of Homozygous Familial Hypercholesterolemia (HoFH)

Table 17. Diabetes-Specific Risk Enhancers That Are Independent of Other Risk Factors in Diabetes

4.2.5. Diabetes in Adults Without Established ASCVD

Figure 9. Adults With Diabetes and Without ASCVD

4.2.6. Secondary ASCVD Prevention

Clinical ASCVD Not at Very High Risk*

Clinical ASCVD at Very High Risk*

Heart Failure With Reduced Ejection Fraction (HFrEF) Due to ASCVD

Figure 10. Clinical ASCVD: Criteria for Defining “At Very High Risk” in Adults

Figure 11. Secondary ASCVD Prevention for Adults at Very High Risk

Figure 12. Secondary ASCVD Prevention for Adults at Not Very High Risk

Table 4. ASCVD Risk Related to Lp(a) Concentrations^*

Table 5. Characteristics of Common Lipid-Lowering Medications to Treat Dyslipidemia* (cont'd)
LDL-C-Lowering Medications

Table 5. Characteristics of Common Lipid-Lowering Medications to Treat Dyslipidemia*
LDL-C-Lowering Medications (cont'd)
LDL-C-Lowering Medications Approved only in HoFH

Table 5. Characteristics of Common Lipid-Lowering Medications to Treat Dyslipidemia* (cont'd)
Triglyceride-Lowering Medications

Table 5. Characteristics of Common Lipid-Lowering Medications to Treat Dyslipidemia* (cont'd)
Triglyceride-Lowering Medications (cont'd)

Table 6. High-, Moderate-, and Low-Intensity Statin Therapy^*

Table 9. Considerations for Referral to a Lipid Specialist^*

Table 11. Salient Features of the American Heart Association PREVENT^TM* Equations

4.2.4.3. Severe Hypercholesterolemia With LDL-C ≥190 mg/dL (4.9 mmol/L)^*

Table 15. Liposorber® (LA-15 System) FDA-Approved Indications for Lipoprotein Apheresis^*

Clinical ASCVD Not at Very High Risk^*

Clinical ASCVD at Very High Risk^*

Table 18. Normal and Elevated Lipid Values in Childhood^*