Summary

The 2026 ACC/AHA multisociety guideline replaces the 2018 cholesterol guideline and broadens scope to dyslipidemias including LDL-C, triglycerides, and Lp(a). Major changes: adoption of PREVENT-ASCVD equations (replacing Pooled Cohort Equations) with new lower risk thresholds; reintroduction of explicit LDL-C and non-HDL-C treatment goals stratified by risk; universal one-time Lp(a) measurement; expanded role for apoB, CAC scoring (including incidental CAC on noncardiac CT), and combination nonstatin therapy (ezetimibe, PCSK9 mAb, bempedoic acid, inclisiran, olezarsen for FCS).

Key Recommendations

Use Martin/Hopkins or Sampson/NIH equation (not Friedewald) to estimate LDL-C on standard lipid profiles in adults and children.
Measure Lp(a) at least once in every adult for ASCVD risk assessment; ≥125 nmol/L (50 mg/dL) is a risk-enhancing factor.
Use PREVENT-ASCVD equations for 10-year risk in adults 30–79 without ASCVD: low <3%, borderline 3–<5%, intermediate 5–<10%, high ≥10%.
Initiate high-intensity statin for primary prevention at 10-year risk ≥10% targeting ≥50% LDL-C reduction, LDL-C <70 and non-HDL-C <100 mg/dL.
Initiate at least moderate-intensity statin at intermediate (5–<10%) risk for ≥30–49% LDL-C reduction, goal LDL-C <100 and non-HDL-C <130 mg/dL.
Use CAC scoring in intermediate or selected borderline-risk adults when LLT decision uncertain; CAC=0 supports deferral (except FH, diabetes, smoker, severe hypercholesterolemia, strong premature ASCVD family history); CAC ≥100 or ≥75th percentile prompts LLT initiation.
Secondary prevention not-very-high-risk: high-intensity statin, goal LDL-C <70 and non-HDL-C <100 mg/dL; very high-risk: add ezetimibe and/or PCSK9 mAb to reach LDL-C <55 and non-HDL-C <85 mg/dL.
In severe hypercholesterolemia (LDL-C ≥190 mg/dL) with clinical ASCVD, add ezetimibe, PCSK9 mAb, or bempedoic acid to maximally tolerated statin to achieve LDL-C <55 mg/dL.
In adults 40–75 with diabetes without ASCVD, prescribe moderate-intensity statin (LDL-C <100, non-HDL-C <130); high-intensity if multiple risk factors (LDL-C <70, non-HDL-C <100).
In CKD stage ≥3 with ASCVD, use high-intensity statin ± ezetimibe ± PCSK9 mAb for ≥50% LDL-C reduction and LDL-C <55 mg/dL.
In PLHIV aged 40–75 on stable ART, initiate statin (preferably pitavastatin) for primary prevention regardless of baseline LDL-C.
For TG ≥1000 mg/dL refer to RDN; for FCS use olezarsen; for ASCVD patients with TG 150–499 mg/dL on statin with LDL-C 41–100 mg/dL, consider icosapent ethyl 4 g/day.
Do not use dietary supplements (fish oil, red yeast rice, garlic, cinnamon, plant sterols, turmeric) to lower LDL-C or TG.
Measure apoB in patients on LLT with ASCVD, CKM syndrome, T2DM, or elevated TG once LDL-C/non-HDL-C goals achieved to detect residual atherogenic particle burden.

Thresholds & Doses

PREVENT-ASCVD risk categories: low <3%, borderline 3–<5%, intermediate 5–<10%, high ≥10% (10-year)
Primary prevention LLT consideration threshold: 10-year risk ≥3% (or 30-year ≥10% in low 10-year risk)
LDL-C goals: very-high-risk ASCVD <55 mg/dL (1.4 mmol/L) and non-HDL-C <85 mg/dL (2.2 mmol/L)
LDL-C goals: high-risk primary prevention/ASCVD not very high risk <70 mg/dL (1.8 mmol/L) and non-HDL-C <100 mg/dL (2.6 mmol/L)
LDL-C goals: borderline/intermediate primary prevention <100 mg/dL (2.6 mmol/L) and non-HDL-C <130 mg/dL (3.4 mmol/L)
High-intensity statin: atorvastatin 40–80 mg or rosuvastatin 20–40 mg → ≥50% LDL-C reduction
Moderate-intensity statin: 30–49% LDL-C reduction (e.g., atorvastatin 10–20 mg, rosuvastatin 5–10 mg)
Severe hypercholesterolemia threshold: LDL-C ≥190 mg/dL (4.9 mmol/L)
Lp(a) elevated: ≥125 nmol/L or ≥50 mg/dL (~1.4× ASCVD risk); ≥250 nmol/L (100 mg/dL) ~2×; ≥430 nmol/L (180 mg/dL) ~4×
hsCRP risk enhancer threshold: ≥2 mg/L on 2 successive occasions
CAC categories (Agatston units): 0, 1–9 minimal, 10–99 mild, 100–299 moderate, 300–999 severe, ≥1000 extensive; CAC ≥100 or ≥75th percentile triggers LLT
Triglyceride categories: persistent ≥150 mg/dL (1.7 mmol/L) moderate; ≥500 mg/dL (5.7 mmol/L) severe; ≥1000 mg/dL (11.3 mmol/L) pancreatitis risk
Icosapent ethyl: 2 g twice daily (4 g/day) for TG 150–499 mg/dL with LDL-C 41–100 mg/dL on statin
Inclisiran: 284 mg SC at baseline, 3 months, then every 6 months; ~48–52% LDL-C reduction
Evolocumab 140 mg SC q2wk; alirocumab 75–150 mg q2wk or 300 mg q4wk; ~45–64% LDL-C reduction
Bempedoic acid 180 mg daily; ~17–24% LDL-C reduction
Ezetimibe 10 mg daily; ~18% monotherapy, +25% added to statin
Evinacumab 15 mg/kg IV q4wk for HoFH; ~49% LDL-C reduction
Olezarsen 80 mg SC monthly for familial chylomicronemia syndrome
Lipid monitoring: 4–12 weeks after initiation/intensification, then every 6–12 months; annually if stable
Pediatric screening: ages 9–11 years universal nonfasting TC/HDL-C; adults every 5 years starting age 19
Statin initiation in FH children: age ≥8 years if LDL-C remains ≥160 mg/dL after lifestyle change; goal ≥50% reduction and LDL-C ≤130 mg/dL (≤100 if additional risk)
Pediatric abnormal LDL-C ≥130 mg/dL; abnormal TG ≥100 (age 0–9) or ≥130 mg/dL (age 10–19)
CAC screening age: men ≥40 y, women ≥45 y
Lipoprotein apheresis FDA criteria: HoFH LDL-C >500; HeFH LDL-C ≥300, or LDL-C ≥70 with CAD/PAD, or Lp(a) ≥60 mg/dL with CAD/PAD

Citations

Section 3.4 / Recommendation — Universal once-in-lifetime Lp(a) measurement
Section 4.2.3.2 / Table 11, Table 12 — PREVENT-ASCVD equations and risk thresholds (replacing PCE)
Section 4.2.3.7 — Primary prevention algorithm by risk category with LDL-C and non-HDL-C goals
Section 4.2.4.3 / Figure 7 — Severe hypercholesterolemia (LDL-C ≥190) management with combination LLT
Section 4.2.6 / Figure 10–12 — Secondary prevention very-high-risk criteria and LDL-C <55 mg/dL goal
Section 4.2.7 / Figure 13 — CAC-stratified LLT intensity (CAC ≥1000, 300–999, 100–299, 1–99, 0)
Section 4.2.9 / Figures 14–17 — Hypertriglyceridemia management including olezarsen for FCS and icosapent ethyl
Section 4.2.10 / Table 4 — Lp(a) thresholds and ASCVD relative risk
Table 5, Table 6 — Lipid-lowering drug classes, doses, and statin intensity definitions
Section 5.1 / Table 25–26 — Medication safety considerations