L17 - Lipids Therapeutics

What is the universal first step in lipid management?

Determine whether the patient has clinical ASCVD. Clinical ASCVD = prior MI/ACS, ischemic stroke/TIA, symptomatic PAD, or coronary/peripheral revascularization. YES → secondary prevention; NO → primary prevention.

What baseline lipid evaluation should every patient receive?

Fasting or nonfasting lipid panel (TC, LDL-C, HDL-C, TG); calculate non–HDL-C = TC − HDL-C (no fasting required; co-primary target); measure Lp(a) at least once in a lifetime; screen for secondary causes before lifelong therapy.

What Lp(a) levels are considered risk-enhancing?

≥125 nmol/L (50 mg/dL) = ~1.4× risk; ≥250 nmol/L (100 mg/dL) = ≥2× risk.

What secondary causes of dyslipidemia should be evaluated?

Uncontrolled diabetes, hypothyroidism, alcohol, obesity, nephrotic syndrome, and offending drugs.

What lifestyle interventions apply to ALL patients?

Diet, physical activity, weight management, tobacco counseling, and alcohol counseling. Health-behavior modification is first-line at every risk level and can be used alone or with medications.

What are the 4 automatic statin triggers in PRIMARY prevention?

LDL-C ≥190 mg/dL → high-intensity statin, ≥50% reduction; diabetes age 40–75 → moderate intensity (high if multiple ASCVD risk factors); CKD stage 3–4 age 40–75 → LDL-lowering therapy; HIV age 40–75 → LDL-lowering therapy. These do NOT require a calculated risk score.

What is the CPR model used when there are no automatic statin triggers?

C = CALCULATE using PREVENT-ASCVD; P = PERSONALIZE using risk-enhancing factors; R = RECLASSIFY/REASSESS using CAC if the treatment decision remains uncertain.

What does PREVENT-ASCVD calculate and in whom?

Used in adults age 30–79 and provides both 10-year and 30-year risk estimates. It replaces the old Pooled Cohort Equations in this pathway.

What are the PREVENT 10-year risk categories?

Low <3%; Borderline 3% to <5%; Intermediate 5% to <10%; High ≥10%.

What factors PERSONALIZE/increase ASCVD risk beyond PREVENT?

Family history of premature ASCVD (men <55, women <65); persistent LDL-C ≥160; elevated Lp(a) or apoB; hs-CRP ≥2; metabolic syndrome; chronic inflammatory disease; HIV; CKD; South Asian ancestry; early menopause <45; preeclampsia; gestational HTN/diabetes; preterm delivery.

When and how is CAC used to reclassify risk?

Consider CAC in men ≥40/women ≥45 with borderline or intermediate risk when the statin decision is unclear. CAC = 0 → may defer/reassess in 3–7 years EXCEPT diabetes, smoking, strong family history, or FH.

How does CAC affect LDL-C goals?

CAC 100–299 → LDL-C <70; CAC 300–999 → <70 (may intensify toward <55); CAC ≥1000 → LDL-C <55 AND non–HDL-C <85 (secondary-prevention-level goals).

How is LOW (<3%) primary-prevention risk treated?

Lifestyle; statin only if LDL-C 160–189 or 30-year risk ≥10%. If triggered, use moderate-intensity statin to lower cumulative exposure.

How is BORDERLINE (3–<5%) primary-prevention risk treated?

LDL-lowering MAY be considered after shared decision-making; moderate-intensity statin (≥30–49% reduction); LDL-C goal <100 and non–HDL-C <130.

How is INTERMEDIATE (5–<10%) primary-prevention risk treated?

LDL-lowering SHOULD be considered; ≥moderate-intensity statin (high intensity at upper end); LDL-C <100 and non–HDL-C <130.

How is HIGH (≥10%) primary-prevention risk treated?

TREAT with high-intensity statin (≥50% LDL-C reduction); LDL-C goal <70 and non–HDL-C <100.

How do you intensify primary-prevention treatment if the patient is not at goal?

1) Confirm adherence and optimize/re-dose statin → 2) add ezetimibe (usual first add-on) → 3) if still above goal in high-risk patients, add PCSK9 mAb or bempedoic acid.

What defines VERY-HIGH-RISK secondary prevention?

≥2 major ASCVD events OR 1 major event + multiple high-risk conditions. Major events = ACS within 12 months, prior MI, ischemic stroke, symptomatic PAD. High-risk conditions = age >65, prior revascularization, current smoker, diabetes, HF, HTN, or LDL-C >100 despite maximally tolerated statin + ezetimibe.

What are the lipid goals for VERY-HIGH-RISK secondary prevention?

LDL-C <55 mg/dL; non–HDL-C <85 mg/dL; optional apoB <55 mg/dL; PLUS ≥50% LDL-C reduction.

What are the lipid goals for ASCVD that is NOT very high risk?

LDL-C <70 mg/dL (many still reach <55); non–HDL-C <100 mg/dL; optional apoB <70 mg/dL; PLUS ≥50% LDL-C reduction.

What is the stepwise treatment for SECONDARY prevention?

1) High-intensity statin: atorvastatin 40–80 mg or rosuvastatin 20–40 mg for ≥50% reduction → 2) if not at goal, add ezetimibe and/or PCSK9 mAb → 3) if still above goal, combine ezetimibe + PCSK9 mAb and/or add bempedoic acid → 4) inclisiran may substitute for PCSK9 mAb if unable to tolerate/obtain mAb or patient prefers twice-yearly dosing.

What is the major 2026 change regarding ezetimibe and PCSK9 inhibitors in secondary prevention?

Ezetimibe is NO LONGER required before a PCSK9 mAb. Choose ezetimibe and/or PCSK9 mAb based on magnitude of LDL-C lowering needed and patient preference.

How are triglycerides classified?

Moderate = 150–499 mg/dL; Severe = ≥500 mg/dL (pancreatitis risk); Very severe = ≥1000 mg/dL.

How are moderate TG 150–499 mg/dL treated?

Treat secondary causes first; statin remains the foundation; follow non–HDL-C or apoB rather than LDL-C. In selected high-risk patients on a statin, consider icosapent ethyl 4 g/day for ASCVD risk reduction.

How are severe/very severe TG ≥500 mg/dL treated?

Treat secondary causes; especially at ≥1000, add fenofibrate/fenofibric acid or prescription omega-3 + very-low-fat diet to prevent pancreatitis. For FCS with TG ≥1000, olezarsen (apoC-III antisense) may be used.

What are the major fibrate/niacin pearls?

Do NOT combine gemfibrozil with a statin due to myopathy/rhabdomyolysis risk → use fenofibrate instead. Fenofibrate requires renal dose adjustment. Niacin is last-line/avoided.

How should lipid therapy be monitored?

Repeat lipid panel 4–12 weeks after initiation or any dose change, then every 3–12 months. Obtain baseline ALT. Baseline CK only with high myopathy risk; check CK if muscle symptoms occur. No routine CK/LFT surveillance in asymptomatic patients.

When is apoB especially useful as a tiebreaker?

Once LDL-C/non–HDL-C goals are met, especially with TG >200 mg/dL, diabetes, or achieved LDL-C <70 mg/dL.

Should statins be stopped for new-onset diabetes or liver concerns?

Do NOT stop a statin for new-onset diabetes. The listed contraindication is active/decompensated liver disease.