2026 ACC/AHA Dyslipidemia Guidelines

What's New in 2026

This guideline retires and replaces the 2018 AHA/ACC Cholesterol Guideline. Key changes include:

Topic	2018 Guideline	2026 Update
Risk Calculator	Pooled Cohort Equations (PCE)	PREVENT-ASCVD equations (ages 30–79); includes HF, CKD inputs; no race variable
Risk Thresholds	Low <5%, Borderline 5–<7.5%, Intermediate 7.5–<20%, High ≥20%	Low <3%, Borderline 3–<5%, Intermediate 5–<10%, High ≥10%
Nonstatin Sequencing	Ezetimibe → PCSK9 mAb	Ezetimibe, PCSK9 mAb, or bempedoic acid (selection by LDL gap + preference); inclisiran added as option
Biomarker Roles	ApoB and Lp(a) mentioned	Universal Lp(a) measurement once in lifetime; apoB as optional treatment target; hsCRP role for residual risk
Subclinical Atherosclerosis	CAC for uncertain decisions	New CAC-based treatment algorithm with specific LDL-C goals by CAC score tier
Diabetes	Moderate-intensity statin for all age 40–75	Age-stratified approach (20–39, 40–75, >75); diabetes-specific risk enhancers; IPE for elevated TG
Secondary Prevention	Very high-risk criteria → ezetimibe → PCSK9i	Expanded criteria; bempedoic acid and inclisiran added; no longer required to try ezetimibe before PCSK9i
New Populations	—	HIV (statin recommended); CKD stage 3+ (specific recs); cancer survivors; CID; pregnancy (updated safety)
HFrEF Without ASCVD	Consider statin (2b)	Statin NOT recommended (3: No Benefit)

Screening & Lipid Testing

Who to Screen

Population	When to Screen	Panel
Children & Adolescents	Ages 9–11 y (universal); age 2+ if FH suspected or high-risk conditions	Fasting or nonfasting lipid panel
Young Adults (18–39 y)	Every 4–6 years if baseline normal; sooner if risk factors. Consider Lifetime ASCVD Risk	Fasting lipid panel preferred
Adults ≥40 y	At least every 5 years; annually if on statin or risk factors	Fasting lipid panel; consider apoB, Lp(a)

Biomarker Testing

Biomarker	When to Order	Thresholds	Clinical Implication
Lp(a)	Once in every adult's lifetime 1	≥50 mg/dL (≥125 nmol/L) = elevated	Risk enhancer; ≥80 mg/dL ~ doubles risk; ≥180 mg/dL ~ 4× risk (≈ HeFH equivalent)
ApoB	When TG ≥150 mg/dL, metabolic syndrome, diabetes, or discordance suspected	Optimal targets: <90, <70, or <55 mg/dL (matches LDL-C goals of <130, <100, <70)	Better measure of atherogenic particle burden than LDL-C when TG elevated
hsCRP	Consider for residual inflammatory risk assessment in patients on optimal LLT	>2 mg/L = elevated; >3 mg/L = high inflammatory risk	Additive risk information; may support intensification of therapy
Non-HDL-C	Always — calculated from standard lipid panel (TC minus HDL-C)	Goals track 30 mg/dL above LDL-C goals	Captures VLDL remnants; preferred over LDL-C when TG ≥150 mg/dL

Pearl: Fasting vs. nonfasting — LDL-C, TC, and HDL-C are minimally affected by fasting status. TG rises 20–30% postprandially. Nonfasting is acceptable for screening; fasting preferred before starting therapy or when TG ≥200 mg/dL.

ASCVD Risk Assessment

PREVENT-ASCVD Equations

The 2026 guideline adopts the PREVENT-ASCVD equations for 10-year risk estimation in adults aged 30–79 without established ASCVD. PREVENT includes kidney function (eGFR) and HbA1c as optional inputs, does not use race, and predicts a broader composite including heart failure. For the classic model, see the PCE Risk Calculator.

Risk Category	PREVENT 10-Year Risk	Approximate PCE Equivalent	Action
Low	<3%	<5%	Lifestyle emphasis; LLT only if risk enhancers + CAC >0
Borderline	3% to <5%	5% to <7.5%	Moderate-intensity statin if risk enhancers present; CAC can reclassify
Intermediate	5% to <10%	7.5% to <20%	Moderate-to-high-intensity statin; intensify if risk enhancers
High	≥10%	≥20%	High-intensity statin; add nonstatin if goals not met

Risk Enhancers

Risk enhancers favor statin initiation or intensification in borderline and intermediate risk patients:

Family history of premature ASCVD (males <55 y, females <65 y)
Persistently elevated LDL-C ≥160 mg/dL (4.1 mmol/L)
Metabolic syndrome
Chronic kidney disease (eGFR 15–59 mL/min/1.73 m²)
Chronic inflammatory conditions (RA, psoriasis, SLE, IBD, HIV)
Reproductive risk markers: premature menopause (<40 y), early menopause (<45 y), preeclampsia, gestational hypertension, gestational diabetes, preterm delivery 2a
High-risk ancestry (e.g., South Asian)
Elevated Lp(a) ≥50 mg/dL (≥125 nmol/L)
Elevated apoB ≥130 mg/dL
Elevated hsCRP ≥2.0 mg/L
ABI <0.9
Elevated TG ≥175 mg/dL (persistent)

CAC Scoring for Risk Reclassification

Consider CAC in borderline (3–<5%) or intermediate (5–<10%) risk patients when the decision to start LLT is uncertain. Use the MESA CHD Risk + CAC Calculator to integrate CAC into risk estimation.

CAC Score (AU)	Interpretation	LDL-C Goal	Management
0	Very low risk	—	Lifestyle only; defer statin up to 5 y (unless diabetes, FH, or smoking)
1–99 & <75th %ile	Mild	<100 mg/dL	Moderate-intensity statin; goal ≥30% LDL-C reduction
≥100 or ≥75th %ile	Moderate	<70 mg/dL	Statin as first-line; ≥50% LDL-C reduction; non-HDL-C <100
≥300	Severe	<70 mg/dL	Treat as secondary prevention equivalent; ≥50% LDL-C reduction
≥1000	Extensive	<55 mg/dL	Treat as very high-risk ASCVD equivalent; non-HDL-C <85

Pearl: A CAC score of 0 has a strong negative predictive value for ASCVD events over 5–10 years, and can support deferring statin therapy. However, CAC = 0 does not exclude noncalcified plaque, especially in younger patients.

CPR Framework: Calculate → Personalize → Reclassify

Systematic Risk Evaluation (Figure 5)

Calculate: Estimate 10-year ASCVD risk with PREVENT-ASCVD. Classify as Low (<3%), Borderline (3–<5%), Intermediate (5–<10%), or High (≥10%). 1

Personalize: Discuss risk estimate and therapy options with patient. 1 In borderline-risk patients, evaluate risk enhancers to personalize the decision. 2a

Reclassify: If clinical or patient uncertainty remains in borderline or intermediate risk, consider CAC scoring and revise risk classification accordingly. 1

Decide & Treat: Low risk → lifestyle modification. 1 Borderline → treat with lifestyle ± LLT. 2a Intermediate/High → lifestyle modification and lipid-lowering therapy. 1

Benefit-Risk Discussion Checklist

Before initiating or intensifying LLT, discuss with the patient:

ASCVD risk estimate and what it means in absolute terms
Potential benefits of therapy (ASCVD event reduction, life-years gained)
Potential harms (myalgias, new-onset diabetes, drug interactions)
Lifestyle modifications and their expected impact on lipids
Costs, adherence burden, and patient preferences
Option to defer and reassess (e.g., after CAC scoring or 3–6 mo lifestyle trial)

When to Refer to a Lipid Specialist

Consider referral when:

Suspected or confirmed familial hypercholesterolemia (LDL-C ≥190 mg/dL or clinical FH criteria)
Homozygous FH or LDL-C >500 mg/dL
LDL-C not at goal despite maximally tolerated statin + ezetimibe + additional agents
Statin intolerance with ≥2 statins and inability to achieve goals with nonstatin therapy
Severe hypertriglyceridemia (TG ≥500 mg/dL) refractory to lifestyle + fibrate
Lp(a) ≥180 mg/dL (~430 nmol/L) with progressive ASCVD
Need for lipoprotein apheresis or advanced therapies (evinacumab, lomitapide)

Lifestyle Management

Lifestyle optimization is the foundation of dyslipidemia management at every risk level and should accompany all pharmacotherapy.

Intervention	Recommendation	Expected LDL-C Reduction
Diet	Mediterranean or DASH pattern; reduce saturated fat to <6% of calories; eliminate trans fats; increase soluble fiber (10–25 g/day) and plant stanols/sterols (2 g/day)	5–15%
Exercise	≥150 min/week moderate-intensity or ≥75 min/week vigorous aerobic activity	3–5% (modest LDL-C effect; improves TG, HDL-C)
Weight Loss	5–10% body weight reduction if overweight/obese	5–8% per 10 kg lost
Alcohol	Limit or eliminate (major contributor to hypertriglyceridemia)	TG reduction 20–30% with elimination
Smoking Cessation	Strongly recommended — independent ASCVD risk factor	Minimal direct LDL-C effect; major CV risk reduction

TG-Specific Dietary Modifications (Figure 2)

For patients with hypertriglyceridemia, additional dietary interventions beyond standard heart-healthy diet:

TG 150–499 mg/dL: Reduce added sugars and refined carbohydrates; limit saturated fat to <7% of calories; increase omega-3-rich foods (fatty fish ≥2 servings/week); limit alcohol to ≤1 drink/day or eliminate
TG 500–999 mg/dL: Restrict total fat to <25–30% of calories; eliminate alcohol completely; avoid concentrated sweets and sugar-sweetened beverages
TG ≥1000 mg/dL: Very-low-fat diet (<10–15% of calories from fat); eliminate alcohol; consider medium-chain triglyceride (MCT) oil as fat substitute

Secondary Causes of Elevated LDL-C (Table 15)

Rule out before attributing hypercholesterolemia to genetics or lifestyle alone:

Dietary: High saturated fat, high cholesterol, high trans-fat intake; rapid weight loss; ketogenic diet
Metabolic: Hypothyroidism, diabetes, nephrotic syndrome, CKD, obstructive liver disease, Cushing syndrome
Medications: High-dose thiazides, glucocorticoids, estrogens, androgens, atypical antipsychotics, cyclosporine, isotretinoin
Physiological: Pregnancy, menopausal transition

Statin Therapy

Statin Intensity & Expected LDL-C Reduction

Use the LDL-C Reduction Calculator to estimate on-treatment LDL-C for different statin + nonstatin combinations.

Intensity	Expected LDL-C Reduction	Medications
High Intensity	≥50%	Atorvastatin 40–80 mg; Rosuvastatin 20–40 mg
Moderate Intensity	30–49%	Atorvastatin 10–20 mg; Rosuvastatin 5–10 mg; Simvastatin 20–40 mg; Pravastatin 40–80 mg; Lovastatin 40–80 mg; Fluvastatin 80 mg; Pitavastatin 1–4 mg
Low Intensity	<30%	Simvastatin 10 mg; Pravastatin 10–20 mg; Lovastatin 20 mg; Fluvastatin 20–40 mg

Nonstatin LDL-C-Lowering Therapies

Drug	Mechanism	LDL-C Reduction	Key Considerations
Ezetimibe	Cholesterol absorption inhibitor	~18–20%	Generic, well-tolerated; first-line add-on; proven CVOT benefit (IMPROVE-IT)
Bempedoic acid	ACL inhibitor (upstream of HMG-CoA reductase)	~18–20%	Prodrug — activated in liver, not muscle; option for statin-intolerant patients; CLEAR Outcomes: 13% MACE reduction
PCSK9 mAb (evolocumab, alirocumab)	PCSK9 inhibition → ↑ LDL receptor recycling	~50–60%	SQ injection q2w or monthly; FOURIER/ODYSSEY CVOT benefit; currently preferred PCSK9i due to CVOT data
Inclisiran	siRNA targeting PCSK9 mRNA	~50%	SQ injection at 0, 3 mo, then q6mo; no completed CVOT yet (ORION-4, VICTORION-2P pending); second-line PCSK9i
Ezetimibe + Bempedoic acid combo	Dual mechanism	~38%	Fixed-dose combination available; useful for statin-intolerant

Treatment Goals Summary

Patient Group	LDL-C % Reduction	LDL-C Goal	Non-HDL-C Goal	ApoB (Optional)
Primary prevention — low-moderate risk	≥30%	<100 mg/dL	<130 mg/dL	<90 mg/dL
Primary prevention — intermediate-high risk	≥50%	<70 mg/dL	<100 mg/dL	<70 mg/dL
Clinical ASCVD — not very high risk	≥50%	<70 mg/dL	<100 mg/dL	<70 mg/dL
Clinical ASCVD — very high risk	≥50%	<55 mg/dL	<85 mg/dL	<55 mg/dL
Severe hypercholesterolemia / FH	≥50%	<70 mg/dL (or <100 with high-risk)	<100 mg/dL	<70 mg/dL

Primary Prevention Algorithm

For adults age 30–79 with LDL-C 70–189 mg/dL (1.8–4.9 mmol/L), no clinical ASCVD, and not on LLT:

Step-by-Step Decision Pathway

Step 1: Calculate 10-year ASCVD risk using PREVENT-ASCVD equations. → Open PREVENT Calculator

Step 2: Assess for risk enhancers and, if decision uncertain, consider CAC scoring.

If PREVENT risk <3% (Low): Lifestyle emphasis. LLT only if risk enhancers present AND CAC >0. If CAC = 0, defer LLT.

If PREVENT risk 3% to <5% (Borderline): Benefit-risk discussion. Start moderate-intensity statin if risk enhancers present. CAC helpful — if CAC = 0, reasonable to defer.

If PREVENT risk 5% to <10% (Intermediate): Start moderate-intensity statin. Goal: ≥30% LDL-C reduction, LDL-C <100, non-HDL-C <130. If ≥10% or multiple risk enhancers → high-intensity statin with ≥50% reduction, LDL-C <70, non-HDL-C <100.

If PREVENT risk ≥10% (High): Start high-intensity statin. Goal: ≥50% LDL-C reduction, LDL-C <70 mg/dL, non-HDL-C <100. If goals not met → add ezetimibe, bempedoic acid, or PCSK9 mAb.

Severe Hypercholesterolemia (LDL-C ≥190 mg/dL)

1 Rule out secondary causes (Table 15: hypothyroidism, nephrotic syndrome, obstructive liver disease, medications). Cascade screen first- and second-degree relatives. Start maximally tolerated high-intensity statin without risk calculation.

Patient Group	Clinical Context	LDL-C Goal	Non-HDL-C Goal	COR
Without FH, ASCVD risk factors, or subclinical atherosclerosis	Statin + ezetimibe, PCSK9 mAb, and/or bempedoic acid	<100 mg/dL	<130 mg/dL	1
With HeFH, ASCVD risk factors, or subclinical atherosclerosis	Statin + ezetimibe, PCSK9 mAb, and/or bempedoic acid; inclisiran if PCSK9 mAb not tolerated	<70 mg/dL	<100 mg/dL	1
With clinical ASCVD	Statin + ezetimibe, PCSK9 mAb, and/or bempedoic acid; inclisiran as 2nd-line PCSK9i	<55 mg/dL	<85 mg/dL	1

Pearl — Genetic Testing: 1 Panel-based genetic testing for FH (LDLR, APOB, PCSK9 variants) is recommended in adults with possible/probable/definite FH to identify highest-risk individuals and facilitate cascade screening. Consider testing if LDL-C 160–189 mg/dL without secondary cause. 2b

Pitfall: Do NOT use PREVENT-ASCVD or PCE risk calculators in patients with FH — they were developed in general populations and significantly underestimate risk in FH. CAC = 0 should NOT be used to defer statin therapy in FH patients.

Homozygous FH (HoFH)

HoFH Management Pathway (Figure 8)

Identify: LDL-C typically >500 mg/dL (untreated); clinical and/or genetic confirmation of HoFH. Start LLT in infancy/early childhood. 1

Step 1: Maximally tolerated statin + ezetimibe. 1

Step 2: Add PCSK9 mAb (evolocumab/alirocumab). Response may be limited due to absent/defective LDL receptors. 2a

Step 3: If LDL-C ≥100 mg/dL despite above → consider evinacumab (ANGPTL3 inhibitor; LDL receptor-independent mechanism). 2b

Step 4: Lomitapide (MTP inhibitor) with hepatic monitoring; lipoprotein apheresis for refractory cases. 2b

Refer: All HoFH patients should be managed in consultation with a lipid specialist. 1

FDA-Approved Lipoprotein Apheresis Criteria (Table 16)

Group	Criteria
A	HoFH homozygotes with LDL-C >500 mg/dL
B	FH heterozygotes with LDL-C ≥300 mg/dL
C	FH heterozygotes with LDL-C ≥70 mg/dL + documented CAD or documented PAD
D	FH heterozygotes with Lp(a) ≥60 mg/dL (or 130 nmol/L) + documented CAD or documented PAD

Secondary ASCVD Prevention

Defining "Very High Risk" ASCVD

Very high risk = any of the following:

≥2 major ASCVD events (ACS within 12 mo, history of MI [other than ACS], ischemic stroke, symptomatic PAD)
OR: 1 major ASCVD event + ≥2 high-risk conditions (age ≥65, prior CABG/PCI, current smoker, diabetes, HF, hypertension, LDL-C ≥100 mg/dL despite maximally tolerated statin + ezetimibe)

Note: The majority of patients with clinical ASCVD are likely to be at very high risk.

Treatment Algorithm — Very High Risk ASCVD

Very High Risk Pathway

Step 1: Start high-intensity or maximally tolerated statin.
Goal: ≥50% LDL-C reduction, LDL-C <55 mg/dL, non-HDL-C <85 mg/dL. Optional apoB <55 mg/dL. 1

Step 2: If goals not met → Add ezetimibe and/or PCSK9 mAb (selection based on LDL-C gap and patient preference). No longer required to try ezetimibe before PCSK9 mAb. 1

Step 3: If unable to tolerate/obtain PCSK9 mAb → Add inclisiran to lower LDL-C. 2a

Step 4: If still not at goal → Add bempedoic acid. 2a

Treatment Algorithm — ASCVD Not at Very High Risk

Not Very High Risk Pathway

Step 1: High-intensity or maximally tolerated statin.
Goal: ≥50% LDL-C reduction, LDL-C <70 mg/dL, non-HDL-C <100 mg/dL. Optional apoB <70 mg/dL. 1

Step 2: If LDL-C <70 and non-HDL-C <100 not achieved → Add ezetimibe, PCSK9 mAb, or bempedoic acid (selection based on degree of LDL-C lowering needed + patient preference). 2a

Step 3: Optional goal: LDL-C <55, non-HDL-C <85, apoB <55 mg/dL. 2a

HFrEF Due to ASCVD

2b In adults with HFrEF attributable to ischemic heart disease, reasonable life expectancy (3–5 years), and not already on a statin because of ASCVD, consider moderate-intensity statin to reduce ASCVD events.

3 In adults with HFrEF who do NOT have clinical ASCVD, statin therapy is NOT recommended to reduce clinical events or mortality.

Diabetes Without Established ASCVD

Age-Stratified Approach

Age Group	Statin Recommendation	Goal	COR
40–75 years	Moderate-intensity statin indicated for ALL	≥30–49% LDL-C reduction; LDL-C <100; non-HDL-C <130	1
40–75 y + multiple ASCVD risk factors	High-intensity statin reasonable	≥50% LDL-C reduction; LDL-C <70; non-HDL-C <100	2a
40–75 y + elevated TG 150–499 + LDL-C <100	Consider adding IPE (icosapent ethyl)	Reduce ASCVD risk	2b
20–39 years	Moderate-intensity statin if diabetes-specific risk enhancers OR PREVENT risk ≥3%/30-y risk ≥10%	Per primary prevention pathway	2a/2b
>75 years	Benefit-risk discussion; moderate-intensity statin reasonable if life expectancy ≥2.5 y	Individualized	2b

Diabetes-Specific Risk Enhancers

These factors are independent of traditional risk enhancers and favor initiating or intensifying statin therapy:

Long duration (≥10 years for type 2 diabetes or ≥20 years for type 1)
Albuminuria ≥30 μg of albumin/mg creatinine
eGFR <60 mL/min/1.73 m²
Retinopathy
Neuropathy
ABI <0.9

Subclinical Coronary Atherosclerosis (CAC-Based Management)

For men ≥40 or women ≥45 years with CAC detected on dedicated or incidental imaging:

CAC Score	Statin Intensity	LDL-C % Reduction	LDL-C Goal	Non-HDL-C Goal	COR
1–99 AU & <75th %ile	Moderate	≥30%	<100 mg/dL	<130 mg/dL	2a
≥100 AU or ≥75th %ile	Statin as first-line	≥50%	<70 mg/dL	<100 mg/dL	1
≥300	Statin as first-line	≥50%	<70 mg/dL	<100 mg/dL	1
≥1000	Statin + add-on LLT	≥50%	<55 mg/dL	<85 mg/dL	1
Incidental mild CAC on noncardiac CT	Moderate	≥30%	<100 mg/dL	<130 mg/dL	2a
Incidental moderate-to-severe CAC on noncardiac CT	Moderate-to-high	≥50%	<70 mg/dL	<100 mg/dL	2a

Management of Hypertriglyceridemia

Persistent hypertriglyceridemia = fasting TG ≥150 mg/dL (1.7 mmol/L) after lifestyle optimization and management of secondary causes for ≥4–12 weeks.

Secondary Causes to Evaluate First

Diseases: Poorly controlled diabetes, CKD/nephrotic syndrome, hypothyroidism, Cushing syndrome, lipodystrophy, hepatitis, SLE, multiple myeloma.

Lifestyle: Alcohol excess, high-sugar/high-fat diets, sedentary lifestyle, obesity.

Medications: Beta-blockers, thiazides, oral estrogens, glucocorticoids, atypical antipsychotics, isotretinoin, HIV protease inhibitors, bile acid sequestrants, immunosuppressants (tacrolimus, sirolimus, cyclosporine).

TG-Stratified Management

TG Level	Context	Management	COR
150–499 mg/dL	No ASCVD or diabetes	Lifestyle first → If persistent, estimate PREVENT risk → statin to achieve LDL-C/non-HDL-C goals	1
150–499 mg/dL	With ASCVD & LDL-C ≤55 on max statin	Intensify LDL-C-lowering therapy (LDL-C lowering remains priority); if LDL-C <100 & non-HDL-C <130 on max statin → consider adding IPE	1 / 2b
≥500 mg/dL	Any	Lifestyle + maximize statin + add fibric acid derivative or Rx omega-3 fatty acids to reduce pancreatitis risk	2a
≥1000 mg/dL (FCS)	Familial chylomicronemia syndrome	Very-low-fat diet (<10–15% fat); olezarsen (apoC-III inhibitor) as adjunct; refer to lipid specialist	1

TG-Lowering Medications (Table 7)

Drug Class	Agents	TG Reduction	Key Considerations
Fibrates	Fenofibrate 48–145 mg/day; Fenofibric acid 45–135 mg/day	20–50%	Use fenofibrate (NOT gemfibrozil) with statins. Adjust dose for renal function. Monitor LFTs.
Rx Omega-3 (EPA+DHA)	Omega-3-acid ethyl esters 4 g/day; Omega-3-carboxylic acids 2–4 g/day	20–30%	For TG ≥500 mg/dL. May raise LDL-C. Monitor for AF. No CVOT benefit (STRENGTH trial).
IPE (EPA only)	Icosapent ethyl 2 g BID	~18%	REDUCE-IT: 25% MACE reduction in ASCVD/DM + TG 150–499. ↑ AF and bleeding risk.
Olezarsen	ApoC-III inhibitor (SQ monthly)	50–80%	For familial chylomicronemia syndrome (FCS) with TG ≥1000 mg/dL. Specialist-initiated.

ASCVD + Hypertriglyceridemia Pathway (Figure 15)

Patients With Clinical ASCVD and Elevated TG

Priority 1: Maximize LDL-C lowering — high-intensity statin ± ezetimibe ± PCSK9 mAb to achieve LDL-C <55 mg/dL (very high risk) or <70 mg/dL. 1

Reassess TG: If TG remains ≥150 mg/dL after LDL-C optimization → evaluate secondary causes, reinforce lifestyle.

If ASCVD + LDL-C ≤55 mg/dL + TG 150–999 mg/dL: Intensify LDL-C-lowering therapy remains first priority. If LDL-C <100, non-HDL-C <130, on maximally tolerated statin → consider adding IPE for residual ASCVD risk reduction. 2b

Hypertriglyceridemia Without ASCVD or Diabetes (Figure 16)

Primary Prevention TG Pathway

Step 1: Lifestyle optimization for ≥4–12 weeks: reduce simple sugars, alcohol, saturated fat; increase exercise; weight loss 5–10%. 1

Step 2: If TG persistent 150–499 mg/dL → Estimate PREVENT-ASCVD risk → Initiate statin to achieve LDL-C/non-HDL-C goals per risk category.

Step 3: If TG persistent ≥500 mg/dL → Add fibrate or Rx omega-3 to reduce pancreatitis risk, even if LDL-C is at goal. 2a

TG ≥500 mg/dL — Urgent Pancreatitis Risk Protocol (Figure 17)

Urgent: TG ≥500 mg/dL carries risk of acute pancreatitis. TG ≥1000 mg/dL is a medical urgency.

Severe Hypertriglyceridemia Management

Immediate: Very-low-fat diet (<10–15% calories from fat if TG ≥1000). Eliminate alcohol completely. Address secondary causes aggressively (uncontrolled diabetes, medications, hypothyroidism). 1

Pharmacotherapy: Fibrate (fenofibrate preferred) ± Rx omega-3 fatty acids to lower TG below 500 mg/dL. Maximize statin if tolerated. 2a

FCS (TG ≥1000 mg/dL, fasting): Olezarsen (apoC-III inhibitor) as adjunct to diet. Refer to lipid specialist. 1

Consider genetic testing if TG persistently ≥500 despite optimal management — may reveal familial hypertriglyceridemia, FCS, or multifactorial chylomicronemia.

TG-Lowering Medication Safety (Table 26)

Medication	Common Side Effects	Key Contraindications	Monitoring
Fenofibrate	GI symptoms, myalgias (rare), ↑ creatinine (reversible), cholelithiasis	Severe renal impairment; active liver disease; concurrent gemfibrozil	LFTs, renal function at baseline and periodically; lipid panel at 4–12 wk
Rx Omega-3 FA	Fishy taste, GI upset, ↑ LDL-C (EPA+DHA formulations)	Fish/shellfish allergy (for some formulations)	Lipid panel; monitor for AF symptoms; LDL-C may rise — reassess
IPE (Icosapent ethyl)	↑ Atrial fibrillation/flutter (~5%), ↑ bleeding, peripheral edema, arthralgia	Hypersensitivity to fish; use caution with anticoagulants	Monitor for AF; bleeding events; lipid panel
Olezarsen	Injection-site reactions, ↑ hepatic transaminases	Specialist initiation only	LFTs, lipid panel, platelet count

Pearl: When TG ≥150 mg/dL, use non-HDL-C or apoB rather than LDL-C for clinical decision-making — LDL-C calculation becomes unreliable with high TG (Friedewald underestimates if TG 150–400; invalid if TG >400).

Pitfall — IPE (Icosapent Ethyl): The REDUCE-IT trial showed 25% MACE reduction but used mineral oil placebo, which may have inflated benefit by raising LDL-C/hsCRP in the placebo arm. STRENGTH trial (carboxylic acid EPA+DHA with corn oil placebo) showed no benefit. Weigh benefits vs. risks (↑ atrial fibrillation, bleeding) carefully.

Approach to Elevated Lp(a)

Use the Lp(a)-Adjusted ASCVD Risk Calculator to incorporate Lp(a) into risk estimation.

Lp(a) Level	Approximate Risk	Management
≥50 mg/dL (≥125 nmol/L)	~40% higher relative risk; affects ~20% of population	Optimize all modifiable risk factors early and aggressively; treat as risk enhancer for statin decisions. 1
≥80–100 mg/dL (200–250 nmol/L)	~doubles ASCVD risk	Intensify LLT; consider PCSK9i (lowers Lp(a) ~15–30% + LDL-C); lipoprotein apheresis for refractory FH + Lp(a) ≥60
≥180 mg/dL (~430 nmol/L)	~4× risk (equivalent to HeFH)	Treat as FH-equivalent; aggressive LDL-C lowering; PCSK9 mAb preferred; refer to lipid specialist

Pearl: Statins do NOT lower Lp(a) — they may modestly increase it (~1 mg/dL). PCSK9 mAb and lipoprotein apheresis are the only approved options that lower Lp(a). Specific Lp(a)-lowering therapies (mRNA-targeting agents) are in clinical trials.

Pitfall: Lp(a) is largely genetically determined and does NOT respond to lifestyle modifications. Focus management on aggressive control of all other modifiable risk factors.

Special Populations

Older Adults (>75 Years)

Scenario	Recommendation	COR
All older adults	Benefit-risk discussion including patient priorities, functional status, multimorbidity, frailty, polypharmacy, and life expectancy	1
Life expectancy ≥2.5 y, no ASCVD	Reasonable to initiate moderate-intensity statin after shared decision-making	2b
Life expectancy <1 y	Reasonable to discontinue LDL-lowering therapy	2b
Uncertain decision, life expectancy ≥2.5 y	CAC scoring may help reclassify — if CAC 0, may defer LLT	2b

CKD Stage 3 or Higher

Estimate renal function: CKD-EPI eGFR | Cockcroft-Gault CrCl

1 Adults 40–75 y with CKD ≥stage 3 and LDL-C 70–189 mg/dL: moderate-intensity statin or moderate statin + ezetimibe (based on SHARP trial). If clinical ASCVD present: high-intensity statin + PCSK9 mAb to LDL-C <55.

2b On hemodialysis: reasonable to continue existing statin; do NOT initiate de novo.

Note: Rosuvastatin doses may need reduction in severe CKD (<30 mL/min) — max 10 mg. Statins with lower renal clearance (atorvastatin) preferred.

Ancestry Considerations (Table 21)

Higher risk groups:

South Asian ancestry: High-risk demographic group and recognized risk enhancer. Increased prevalence of diabetes at lower BMI.
Filipino ancestry: Increased CKM syndrome risk factors including hypertension, hyperlipidemia, and obesity.
Native Hawaiian / Pacific Islander: Higher CVD mortality compared with other Asian Americans.

Lipid variations: Higher Lp(a) levels in non-Hispanic Black individuals (CVD relative risk similar to other groups). Elevated Lp(a) is a higher population-attributed risk for MI in South Asian and Latin American people.

Statin sensitivity: Some individuals of Chinese, Japanese, or Korean ancestry have higher plasma concentrations of rosuvastatin — may benefit from starting at a lower dose.

HIV

1 In people living with HIV aged 40–75 on stable antiretroviral therapy, statin therapy is recommended (based on REPRIEVE trial — pitavastatin showed 35% MACE reduction). Pitavastatin preferred (minimal CYP3A4 interactions). If using other statins, check drug-drug interactions with antiretrovirals carefully.

Key ART–Statin Interactions (Table 22)

ART Class	Safe Statins	Avoid / Dose-Limit
Protease Inhibitors (atazanavir, darunavir, lopinavir)	Pitavastatin (no adjustment); Pravastatin (monitor)	Lovastatin, Simvastatin — CONTRAINDICATED. Atorvastatin — do not exceed 20 mg/day. Rosuvastatin — do not exceed 10 mg/day.
NNRTIs (efavirenz, etravirine, nevirapine)	Pitavastatin (no adjustment); Rosuvastatin (no adjustment); Atorvastatin (adjust per lipid response)	Dose adjustments may be needed based on lipid response. Do not exceed max recommended dose.
INSTIs (dolutegravir, raltegravir, bictegravir)	Most statins — no dose adjustment needed	Elvitegravir/cobicistat: treat as protease inhibitor — lovastatin/simvastatin contraindicated; limit atorvastatin 20 mg/day.
NRTIs (all)	All statins — no dose adjustment needed	—

Pregnancy & Lactation

Medication	Pregnancy	Lactation
Statins	Discontinue 1–2 mo before conception; can be considered in very high-risk (FH, ASCVD history)	Avoid
Bile acid sequestrants	Safe (no systemic absorption); consider if LDL-C ≥300 during pregnancy	Caution (fat-soluble vitamin malabsorption)
Ezetimibe, PCSK9 mAb, bempedoic acid, inclisiran	Avoid — insufficient data	Avoid
Fibrates / Omega-3	Consider for severe hypertriglyceridemia (TG ≥500) after first trimester	Avoid fibrates; omega-3 caution

Children & Adolescents (Tables 18–19)

Screening: Universal lipid screening at ages 9–11 y and again at 17–21 y. Screen at age ≥2 y if FH suspected, high-risk conditions, or family history of premature CVD.

1 Lifestyle management is first-line for all children with lipid abnormalities (≥3–6 months trial).

1 In children ≥8 y with LDL-C persistently ≥160 mg/dL consistent with FH, after lifestyle trial: initiate statin. FDA-approved statins in pediatrics: rosuvastatin (≥8 y), atorvastatin (≥10 y), pravastatin (≥8 y), fluvastatin (≥10 y).

2a Panel-based genetic testing for FH guides diagnosis, cascade screening, and treatment selection.

LDL-C goals in children with FH: ≥50% reduction from baseline; target <130 mg/dL (or <100 mg/dL if additional risk factors). Add ezetimibe if statin alone insufficient. PCSK9 mAb (evolocumab) FDA-approved ≥10 y for HeFH.

Cancer Survivors

1 Cancer survivors with life expectancy ≥2 years who otherwise qualify for LLT should be treated the same as those without cancer history. Continue statins in patients with active cancer unless DDI or life expectancy <1 year.

2b Statins may be considered before anthracycline chemotherapy to prevent cardiotoxicity.

Chronic Inflammatory Diseases

Adults with RA, psoriatic arthritis, SLE, IBD, and other CID have elevated ASCVD risk. Standard risk calculators may underestimate risk. Lipid monitoring is recommended, especially after changes in anti-inflammatory therapy. Statins can be used safely; anti-inflammatory therapies (glucocorticoids, hydroxychloroquine) can also modify lipid profiles.

Statin-Attributed Muscle Symptoms

Risk Factors for Muscle Symptoms

Age ≥65, low BMI, female sex, obesity, hypothyroidism, diabetes, chronic liver/kidney disease, alcohol use, vigorous exercise, high-dose statin therapy, drug interactions, and genetic factors (SLCO1B1).

Management Algorithm

Approach to Muscle Symptoms (on ≥2 statins, 1 at lowest dose)

Step 1: Benefit-risk discussion. Evaluate secondary causes of muscle symptoms. If severe myalgias or weakness → measure CK. 1

Step 2 — With clinical ASCVD: Add reduced-dose statin (if tolerated), bempedoic acid, ezetimibe, and/or PCSK9 mAb. Goal: LDL-C per ASCVD goals. If unable to achieve goals on bempedoic acid ± ezetimibe → inclisiran. 1

Step 2 — Without ASCVD, high risk (PREVENT ≥10% or CAC ≥300 or diabetes): Add bempedoic acid and/or ezetimibe or PCSK9 mAb. Goal: LDL-C <70, non-HDL-C <100. 1

Step 2 — Without ASCVD, borderline-intermediate risk (PREVENT 3–<10%): Consider ezetimibe and/or bempedoic acid. Goal: LDL-C <100, non-HDL-C <130. CAC may help decision-making. 2b

✓ DO

Acknowledge patient concerns while reinforcing ASCVD risk of stopping therapy
Try alternate statin, lower dose, or less-than-daily dosing (rosuvastatin or atorvastatin with longer half-lives)
Use bempedoic acid — it is a prodrug activated in the liver, not skeletal muscle
Consider CAC in uncertain primary prevention cases to guide whether nonstatin therapy is warranted

✗ DO NOT

Routinely measure CK in asymptomatic patients (3: No Benefit)
Routinely measure hepatic transaminases in patients without hepatotoxicity symptoms (3: No Benefit)
Use coenzyme Q10 to treat or prevent statin muscle symptoms (3: No Benefit)

Statin-Cardiovascular Drug Interactions

1 Before initiating statin therapy, review concomitant medications for potential DDI to minimize risk of adverse events.

Key CYP-Mediated Interactions

Interacting Drug	Statins Affected	Management
Gemfibrozil	ALL statins	AVOID combination with any statin (↑ risk of rhabdomyolysis). Use fenofibrate if fibrate needed.
Diltiazem	Lovastatin, Simvastatin	Limit lovastatin to 20 mg/day; simvastatin to 10 mg/day. Or switch statin.
Amiodarone	Lovastatin, Simvastatin	Limit lovastatin to 40 mg/day; simvastatin to 20 mg/day.
Dronedarone	Lovastatin, Simvastatin	Limit lovastatin to 10 mg/day; simvastatin to 10 mg/day.
Ticagrelor	Lovastatin, Simvastatin	Limit lovastatin/simvastatin to 40 mg/day. Atorvastatin acceptable without dose limit.
Colchicine	All (esp. atorvastatin, fluvastatin)	Closer monitoring for muscle toxicity recommended.
HIV Protease Inhibitors	Lovastatin, Simvastatin (contraindicated); Atorvastatin (limit dose)	Pitavastatin or pravastatin preferred (minimal CYP3A4 metabolism).

Safety of LDL-C-Lowering Medications

Medication Class	Common Side Effects	Key Contraindications	Monitoring
Statins	Myalgias (common, dose-related); rhabdomyolysis (very rare)	Decompensated cirrhosis; severe NM disease; pregnancy/lactation	CK only if symptomatic; lipid panel 4–12 wk after starting then annually; hepatic transaminases NOT routine
Ezetimibe	Usually well tolerated; rare myalgias, fatigue, diarrhea	Prior hypersensitivity; caution with moderate-severe hepatic impairment	Monitor hepatic transaminases before and after statin combo initiation
Bempedoic acid	Well tolerated; ↑ BUN, creatinine, uric acid	Prior hypersensitivity	Monitor urate in patients with gout/hyperuricemia
PCSK9 mAb	Injection-site reactions; rare hypersensitivity/angioedema	Prior hypersensitivity	Lipid panel 4–12 weeks after initiation
Inclisiran	Injection-site reactions	Prior hypersensitivity	Lipid panel before each dose (q6 mo after loading)