Dyslipidemia-come back to memorize intensity

Distinguish between primary and secondary prevention of CVD

• Primary: no history of ASCVD → preventing future events 

  • Increased risk of a primary cardiovascular event 

• Secondary:  established clinical ASCVD → already had an event + trying to prevent future events 

  • Goal is to prevent a secondary cardiovascular event

• * Clinical ASCVD = ACS, history of MI, stable or unstable angina, coronary or other revascularization, stroke, TIA, PAD

Identify modifiable and non-modifiable CV risk factors 

• Modifiable: 

  • HTN (BP > 140/90)

  • “Dyslipidemia”

    • High TC, TG, or LDL

      • Only 15% is related to diet

      • Drug therapy not routinely indicated until Triglycerides (TG) > 500-1000 mg/dL

        • Also common in diabetes, so not often treated in these patients 

    • Low HDL (< 40 mg/dL)

      • Exercise and diet is the best ways to increase HDL → no primary drug therapy 

    • obesity/ inactivity

    • Diabetes

    • Metabolic syndrome 

    • Smoking 

• Non-modifiable: 

  • Age

    • Males > 45 yr

    • Females > 55 yr

    • Family hx/o CVD

      • Male first-degree relative < 55 yr

      • Female first degree relative < 65 yr 

• Other CV Risk factors - not LO

  • Carotid intima media thickness

  •  Coronary calcium score

  • Apolipoprotein B (ApoB)

  • Lipoprotein A - Lp(a)

  • hsCRP

Lipid Profile and CVD Risk

Recall key lifestyle (diet & physical activity) recommendations to reduce CV risk

• Important to intake vegetables, fruits, legumes, nuts, whole grains, and fish is recommended to decrease ASCVD risk factors 

• Exercise for at least 150 minutes per week (moderate intensity) or 75 minutes per week( vigorous-intensity) 

• Weight loss 

• Alcohol consumption in moderation

  • 1 drink for women or 2 drinks a day for men maximum 

4 Statin Benefit Groups

1. Clinical ASCVD “Secondary Prevention”

2. LDL > 190 mg/dL

3. Diabetes Mellitus Age 40-75

4. No Diabetes Mellitus Age 40-75; LDL 70-189

Clinical ASCVD “Secondary Prevention”

  LDL > 190 mg/dL  

Diabetes Mellitus Age 40-75 ( primary prevention)

No Diabetes Mellitus Age 40-75; LDL 70-189

Groups 2-4 (LDL, Non/Diabetics)

Atorvastatin 40-80 mg

High-Intensity Statin

Rosuvastatin 20-40 mg

High-Intensity Statin

Atorvastatin 10-20 mg

Moderate-Intensity Statin

Rosuvastatin 5-10 mg

Moderate-Intensity Statin

Simvastatin 20-40mg

Moderate-Intensity Statin

Pravastatin 40-80mg

Moderate-Intensity Statin

Lovastatin 40mg

Moderate-Intensity Statin

Simvastatin 10mg

Low-Intensity Statin

Pravastatin 10-20mg

Low-Intensity Statin

Lovastatin 20mg

Low-Intensity Statin

1st line treatment for LDL reductions and primary and secondary prevention of CV events 

• Clinical effects: decrease LDL, TG;  maintenance or increase of HDL

• Monitoring

  • Fasting Lipid panel

    • Baseline

    • 4-12 weeks after starting/changing dose to assess for % LDL reduction 

  • CK

    • Baselines and if experiencing myotoxicity 

  • Liver Function 

    • Baseline and if clinically indicated

  • Pregnancy 

    • Category x, teratogenic 

HMGCoA-Reductase Inhibitors (Statins)

prevents the absorption or cholesterol from the intestine

• acts act the brush bored of the small intestine to inhibit cholesterol absorption 

• Clinical effects: decreases LDL, decreases/maintains TG, increases and maintains HDL

• When added to statin, can further reduce LDL by 13-20%

• Group 1 and 2 high risk groups → added to statin to decrease LDL low

Ezetimibe

(more expensive - usually last because of cost)

• PCSK9 binds to LDL receptors and target them for lysosomal degradation

  • Too much PCSK9 activity leads to fewer LDL receptors on surface and increases LDL levels in blood

• Clinical effects: big decrease in LDL, maintenance HDL and TG

  • Highest efficacy in LDL response 

• Place in therapy:

  • Addition to max-tolerated statin if unable to achieve adequate LDL response

  • Very costly, brand name

  • Injectable

  • When added to statin, can further reduce LDL by 43-64%

PCSK9-Inhibitor

• Clinical effects: decrease in LDL/TG; increase in HDL

• Place in therapy:

  • ACC/AHA guidelines make no formal recommendation for use

  • Evidence does not suggest additional benefit is already taking statin 

• Adverse effects:

  • Flushing and Pruritus

  • Hyperuricemia

  • Hyperglycemia 

Niacin

• Clinical effects: decrease LDL, increase/maintain HDL and TG

• Place in therapy: 

  • when added to statin can further reduce LDL by 15-30%

  • Second line after ezetimibe or PCSK9

• Counseling:

  • GI intolerance, many drug interactions, fat-soluble vitamin deficiency

  • Administer 2 hours before or 4-6 hours other scheduled meds

Bile Acid Sequestrants

• Indicates as adjunctive therapy to lifestyle modification and statine therapy for treatment of primary hyperlipidemia in adults with heterozygous familial hypercholesterolemia (HeFH) or ASCVD who require additional LDL lowering 

• Lowers LDL cholesterol levels by about 23% compared with placebo

Bempedoic acid

• Indicated as adjective therapy to lifestyle modification and statin therapy for treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or ASCVD who require additional LDL lowering 

• SQ injection given every 3-6 months

• Lowers LDL cholesterol levels by about 50-55% compared with placebo 

Inclisiran

• Indicated as adjective therapy to lifestyle modification and statin therapy for treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or ASCVD who require additional LDL lowering 

• Monthly IV infusion 

• Lowers LDL cholesterol levels by about 47-50% compared with placebo 

Evinacumab

• Clinical effects: decrease/maintain LDL, increase HDL, major decrease in TG

• Place in therapy:

  • Target lowering of TG

  • Not for LDL lowering 

Fibrates

• Clinical effects: maintain LDL, increase HDL, major decrease TG

• Place in therapy:

  • Targeted lowering of TG

  • Not for LDL lowering

  • Requires 2-4 g/day of EPA + DHA

• OTC “fish oil”

• Evidence support in decreased CV events with Vascepa

• Inconsistent evident for general C benefits with OTC fish oil

Omega-3 Fatty Acids 

Treatment for Hypertriglyceridemia

1. If TG >500 mg/dL

   1. Treat lifestyle and secondary causes first

   2. Consider statin therapy is ASCVD risk > 7.5%

   3. Consider omega-3 fatty acids or fibrate

2. If TG >  1000 mg/dL

   1. Start omega-3 fatty acids or fibrate to prevent acute pancreatitis

   2. Takes prior over statin recommendations

Treatment options

• Omega-3 fatty acids

• Lovaza

• Vascepa

• Fenobrate

• Gemfibrozil