Cardiovascular · Topic 37 of 48

Dyslipidemia

Cardiovascular · lipids and ASCVD prevention

Dyslipidemia

LDL goals are back: statin first, sized to risk — LDL-C under 55 mg/dL for very-high-risk ASCVD — then add nonstatins until the goal is met.

Key numbers

High-intensity statin lowers LDL-C ≥ 50%LDL-C ↓ ≥ 50%

ASCVD goal: LDL-C under 55 mg/dLLDL-C < 55 mg/dL

LDL-C ≥ 190: high-intensity statinLDL-C ≥ 190 mg/dL

PREVENT 10-year risk sets the LDL goalrisk ≥ 10% → LDL < 70

Triglycerides ≥ 1,000: treat to prevent pancreatitisTG ≥ 1,000 mg/dL

01 · GiveHigh-intensity statin lowers LDL-C ≥ 50%

High-intensity statins — atorvastatin 40–80 mg or rosuvastatin 20–40 mg daily — lower LDL-C by ≥ 50% and are first-line for clinical ASCVD, LDL-C ≥ 190 mg/dL and high-risk patients.

02 · Defined byASCVD goal: LDL-C under 55 mg/dL

2026 ACC/AHA secondary prevention: LDL-C goal < 55 mg/dL (non-HDL-C < 85) for very-high-risk ASCVD — most patients with ASCVD — and at least < 70 mg/dL for ASCVD not at very high risk.

03 · The ruleLDL-C ≥ 190: high-intensity statin

LDL-C ≥ 190 mg/dL: exclude secondary causes, evaluate for familial hypercholesterolemia (genetic testing), and start a high-intensity statin regardless of calculated risk; goal LDL-C < 100 mg/dL, adding ezetimibe or other nonstatins as needed.

What it is

Core idea

Very high risk: two events, or one plusVery-high-risk ASCVD means a history of two or more major ASCVD events, or one major event plus two or more high-risk conditions; these patients get the LDL-C goal of < 55 mg/dL.

Causes & risk factors

Why it happens

Measure Lp(a) once in every adultMeasure lipoprotein(a) at least once in every adult; ≥ 125 nmol/L (50 mg/dL) is a risk enhancer (about 1.4-fold risk) that calls for more intensive LDL-C lowering.

Rule out secondary causes before treatingSecondary dyslipidemia: diabetes, CKD, hypothyroidism, cholestatic liver disease, alcohol overuse, and drugs such as thiazides, glucocorticoids, retinoids, antiretrovirals, cyclosporine and tacrolimus.

Diagnosis & monitoring

Work-up

PREVENT 10-year risk sets the LDL goal must knowPrimary prevention uses 10-year PREVENT-ASCVD risk (ages 30–79): low < 3% (lifestyle); borderline 3– < 5% and intermediate 5– < 10% (consider therapy; LDL-C goal < 100); high ≥ 10% (treat; goal < 70 mg/dL).

Muscle symptoms: check CK, hold, rechallengeMuscle symptoms occur in up to 10% on statins, often with a normal CK; stop the statin for markedly elevated CK or suspected myopathy, then rechallenge at a lower dose or switch statins.

Baseline liver enzymes; serious hepatotoxicity is rareConsider liver enzymes before starting a statin and recheck only when clinically indicated; serious liver injury is rare, but statins are contraindicated in acute liver failure or decompensated cirrhosis.

Management

Orders

Not at goal: add ezetimibe, bempedoic acid, PCSK9iIf LDL-C is above goal on a maximally tolerated statin, add ezetimibe, bempedoic acid and/or a PCSK9 monoclonal antibody — ezetimibe no longer has to come first; inclisiran is a further option.

Moderate-intensity statin lowers LDL-C 30–49%Moderate-intensity statins (atorvastatin 10–20 mg, rosuvastatin 5–10 mg, simvastatin 20–40 mg, pravastatin 40–80 mg) lower LDL-C 30–49%; used for lower-risk primary prevention or when high intensity is not tolerated.

Bempedoic acid for statin intoleranceBempedoic acid works upstream of HMG-CoA reductase in the liver, does not cause myalgia and lowers cardiovascular events in statin-intolerant patients; it can raise uric acid (gout) and cause tendon rupture.

Red flags & don'ts

Avoid harm

CYP3A4 inhibitors and gemfibrozil raise myopathy risk interactionStatin myopathy and rhabdomyolysis are most likely with CYP3A4 inhibitors (macrolides, azole antifungals, cyclosporine) and with fibrates, especially gemfibrozil; fenofibrate is the safest fibrate to combine with a statin.

Stop statins in pregnancy avoidStop the statin when pregnancy is recognized (except rare very-high-risk cases); bile acid sequestrants are the lipid drugs of choice for patients who are or plan to become pregnant.

Triglycerides ≥ 1,000: treat to prevent pancreatitis complicationTriglycerides > 500 mg/dL raise the risk of acute pancreatitis; at ≥ 1,000 mg/dL start triglyceride-lowering therapy (fibrate) with diet and alcohol restriction, while statins remain the base for ASCVD risk.

The rules

Know these

Diabetes, CKD 3–4 or HIV at 40–75: treat must knowAdults aged 40–75 with diabetes, CKD stage 3–4 or HIV should receive LDL-lowering therapy (at least moderate-intensity statin) regardless of LDL-C level or calculated risk.

Non-HDL-C goal is LDL goal plus 30Non-HDL-C goals run 30 mg/dL above the LDL-C goals: < 85 (very high risk), < 100 (high risk) and < 130 mg/dL (borderline or intermediate risk).

Coronary calcium score reclassifies uncertain riskWhen the statin decision is uncertain at borderline or intermediate risk, a coronary artery calcium score of 0 allows deferring therapy, while ≥ 100 (or ≥ 75th percentile) favors a statin, often high intensity.

High- or moderate-intensity statin?

Commonly confused

LDL-C lowering	≥ 50%
Atorvastatin	40–80 mg
Rosuvastatin	20–40 mg
Typical use	Clinical ASCVD, LDL-C ≥ 190, high risk

More detail

Reference

Show 6 reference facts

PCSK9 monoclonal antibodies (evolocumab, alirocumab) are subcutaneous injections once or twice monthly that lower LDL-C 40–70% and reduce events; inclisiran, an siRNA, is injected every 6 months.

Ezetimibe blocks intestinal cholesterol absorption and lowers LDL-C about 15–20% with few adverse effects; bempedoic acid adds about 15–17%.

Icosapent ethyl 4 g daily reduced cardiovascular events when added to a statin in high-risk patients with triglycerides > 150 mg/dL; fenofibrate is used for substantial triglyceride lowering.

Statins can modestly raise HbA1c and fasting serum glucose, a labeled warning to keep in mind when monitoring patients with prediabetes or diabetes.

Tendon xanthomas (Achilles, extensor tendons of the hands) are a classic sign of familial hypercholesterolemia; eruptive xanthomas and lipemia retinalis signal severe hypertriglyceridemia.

LDL lowering remains beneficial after age 75; continuing or starting therapy is a shared decision weighing risk, comorbidity and patient preference.

Pearl

Lower for longer: the LDL-C a patient lives at, for how many years, is what drives plaque — so treat to a number, starting with a statin.

Sources · Merck Manual Professional — Dyslipidemia · Guideline Central — 2026 ACC/AHA Management of Dyslipidemia Guideline: 10 Key Highlights · ACC — Lower Sooner: How the 2026 Dyslipidemia Guideline Changes Practice · Healio — Top 10 practice takeaways from the 2026 dyslipidemia guideline · EBSCO EBM Focus — Top takeaways from the updated ACC/AHA guideline on management of dyslipidemia · Lipitor (atorvastatin) prescribing information — DailyMed · Blumenthal RS, Morris PB et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia. Circulation 2026 · Morris & Dickson — Cholesterol Management in 2026: What's Changed (statin intensity ranges) · HCPLive — Understanding the 2026 dyslipidemia guidelines: new recommendations on FH and high triglycerides (writing-committee interview) · Valley Medical Center clinician news — 2026 ACC/AHA Dyslipidemia Guidelines: Key Updates for Clinical Practice (LDL-C goal table) · AAFP Community Blog — Updated Guidelines on the Management of Dyslipidemia (2026) · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).