Lipids

Background

1º prevention: pts at increased risk who have not yet had a vascular event
2º prevention: pts with pre-existing occlusive vascular disease or ASCVD (e.g. stroke, TIA, CAD + angina, ACS, coronary or arterial revascularization, PAD)
Screening: All adults ≥ 20y
- USPSTF 2016 Guidelines: q5years for adults 40-75yrs
- ACC/AHA 2019 Guideline: adults 20-39 q4-6yrs; <21yrs if strong fam hx; 40-75 “routinely” assess CV risk and calculate ASCVD risk (dot phrase .ASCVD2013)

Fasting not routinely needed unless evaluating for hyperTG; if non-fasting TG >440, then obtain 12-14h fasting panel
Consider 2º causes of HLD in initial workup: hypothyroidism, DM, EtOH use, smoking, liver disease, nephrotic syndrome, CKD, meds (e.g. thiazide, glucocorticoids)
In pts with borderline ASCVD risk (5%-7.5% risk) or hesitant to take statins with low risk, CAC score can help with shared decision making. Therapy is recommended.
Check lipoprotein(a) (once in a lifetime) in pts with personal or family history of ASCVD, or in pts with less than expected LDL lowering after starting a statin.

Lifestyle changes: weight loss, exercise, smoking cessation, limiting alcohol
- Diet low in sat. fat a/w 15-20 mg/dL ↓ in LDL-C, ~50% ↓risk of CAD
- Diet Avoiding: trans/saturated fats (red meat, processed meat, butter, cheese), sodium (<2300 mg/day) and sugar-sweetened foods and beverages
- Diet Emphasizing: vegetables, fruits, legumes, lean protein, whole grains, nuts

Check AST/ALT prior to initiation
Note that ASCVD risk equation is best validated for non-Hispanic whites and blacks. Consider use of additional risk prediction tools/factors in other pt populations
Lipid panel should be checked 6-8 weeks following initial statin to ensure LDL-C has fallen 30- 50%. After this, consider checking lipid panel yearly to assess adherence.

Statin Potency		Statin Properties
High-Intensity (≥50% ↓LDL-C)	Atorvastatin 40-80 mg Rosuvastatin 20-40 mg	Safest in CKD: atorva, fluva (no renal dose adj.required) Safest in cirrhosis: prava Lowest rate of myopathy: prava, fluva, pitava Lower overall s.e.: prava, rosuva (both hydrophilic) Biggest Change in LDL: rosuvastatin > atorvastatin > simvastatin
Moderate-Intensity (30-49% ↓LDL-C)	Atorvastatin 10-20mg Rosuvastatin 5-10mg Simvastatin 20-40mg Pravastatin 40-80mg Lovastatin 40-80mg Fluvastatin XL 80mg Fluvastatin 40mg BID Pitavastatin 1-4mg
Low-Intensity (<30% ↓LDL-C)	Simvastatin 10mg Pravastatin 10-20mg Lovastatin 20 mg Fluvastatin 20-40mg
Dosing with RCT-proven LDL-lowering benefit is bolded*

Spectrum of statin associated muscle symptoms (SAMS) include myalgias, myopathy, rhabdomyolysis, autoimmune myopathy
- Myalgias: bilateral involving large muscle groups, onset within weeks of initiation of therapy and should resolve within weeks of cessation; CK should be normal
- Consider evaluation with CK, BMP, TSH, and vitamin D
- "ACC Statin Intolerance Calculator” can help assess etiology of symptoms

If pt is not tolerating a statin, consider
- Holding statin until symptoms resolve and trialing lower dose or other statin
- Every other day dosing with rosuvastatin (longer half-life and hydrophilic)
- If repeated failed attempts, consider ezetimibe, PCSK9 inhibitor
Consider adding ezetimibe if pt has very high ASCVD and LDL >70 while on maximally tolerated high-intensity statin
PCSK9 inhibitor requires referral to Lipid Clinic

Moderate: TG 175-499 mg/dL; Moderate-severe 500 - 999; Severe: TG > 1000
Focus on addressing lifestyle factors and stopping medication that increase TG’s (HCTZ, some BB’s, estrogens, some ART, antipsychotics)
Consider medical therapy when TG> 500mg/dL (increased risk of pancreatitis)
- Omega-3-fatty acids (icosapent ethyl) 4gms daily or Vascepa 4gm daily
- Fibrates: fenofibrate 120 mg daily (avoid in CKD), gemfibrozil 600mg BID (increased risk of myopathy with concomitant statin)

Lowest LDL goal recognized for VA Criteria for Use is 100
Preferred statins: atorvastatin, simvastatin, lovastatin
Statins that require PADR: pravastatin, rosuvastatin (2nd-line high-intensity statin)
- Must have documented intolerances or DDI to all preferred statins
Other agents that require PADR
- Ezetimibe
  - Pt has tried and failed or not tolerated all statins (allergy, AE, etc.)
  - Pt not meeting goal on max dose of statin PLUS bile acid sequestrants or niacin
- Fenofibrate
  - Pt has tried all formulary alternatives or has contraindication to use of formulary alternatives (statin, niacin, gemfibrozil, cholestyramine, fish oil)
  - If TG > 500 mg/dL, fenofibrate should be approved