Dyslipidemia Treatment

LDL-C-Lowering Pharmacological Therapy 

LDL-C is the primary target of lipid management 

• The greater the LDL-C level is reduced, the more significant is the amount of CV risk reduction
• Assess patient’s response to LDL-C-lowering therapy and lifestyle modifications with a repeat lipid profile 4-12 weeks after starting statin therapy or dose adjustment then every 3-12 months as needed

Statins (Beta-hydroxy-beta-methylglutaryl-Coenzyme A [HMG-CoA] Reductase Inhibitors) 

• Reduce risk for acute coronary syndromes, coronary procedures and other coronary outcomes in both primary and secondary coronary heart disease prevention
• Recommended for the following:
  • Adults ≥21 years old with clinical atherosclerotic cardiovascular disease (ASCVD)
  • Adults ≥21 years old with LDL-C ≥190 mg/dL
  • Adults 40-75 years of age without ASCVD but with diabetes mellitus (especially type 2 diabetes mellitus) and LDL-C levels of 70-189 mg/dL
  • Adults 40-75 years of age without ASCVD and diabetes mellitus but with LDL-C levels of 70-189 mg/dL and estimated 10-year risk of ≥7.5% for ASCVD
    • If decision to start statin therapy is uncertain, measure coronary artery calcium (CAC); statin therapy is favored with a CAC score of 1-99 and is indicated with a CAC score of ≥100 Agatston units or ≥75th percentile
  • Adults 40-75 years of age without diabetes mellitus but with risk-enhancing factors and estimated 10-year ASCVD risk of 7.5-19.9%
• It is reasonable to initiate statin therapy in patients 20-39 years old with longstanding diabetes or to continue moderate- or high-intensity statin therapy in patients >75 years old with diabetes 
• Effective in patients with nephrotic syndrome
• Inhibit HMG-CoA reductase which is the rate-limiting step in cholesterol biosynthesis
• Most effective class of drugs at lowering LDL-C levels, with moderate effects on lowering TG and elevating HDL-C: Decreases LDL-C in a dose-dependent manner by 20-55%, decreases TG by up to 35%, increases HDL-C by 2-10%
• The drugs of choice for LDL lowering and in reducing CVD risk in high-risk patients (eg DM) with hypertriglyceridemia
  
  • Statin dose may be increased or a non-statin drug (eg Ezetimibe, fibrates, or Nicotinic acid) may be added if TG levels remain at >2 mmol/L (>200 mg/dL) after achieving the LDL-C target level

• High-intensity statins: Atorvastatin (80 mg), Rosuvastatin (20 mg)
  
  • Statin regimen that helps lower LDL-C by ≥50%
  • Recommended to be given at the highest tolerated dose to achieve the LDL-C goals set for a specific risk group
  • Recommended as 1st-line treatment for patients ≤75 years old with clinical ASCVD
  • May be used for patients ≥21 years old with LDL-C ≥190 mg/dL or TG ≥500 mg/dL especially those trying to achieve at least 50% LDL-C level reduction
    
    • A non-statin drug may be added if LDL-C goal has not been achieved with high-intensity regimen
  • For ≥75-year-old patients with ASCVD without contraindications
  • For 40-75-year-old patients with diabetes mellitus with ≥7.5% 10-year ASCVD risk¹
  • For 40-75-year-old patients with diabetes mellitus or LDL-C ≥190 mg/dL

• Moderate-intensity statins: Atorvastatin (10 mg), Rosuvastatin (10 mg), Simvastatin (20-40 mg), Pravastatin (40 mg), Lovastatin (40 mg), Fluvastatin (40 mg 12 hourly), Pitavastatin (1-4 mg)
  • Daily dose helps lower LDL-C by 30-49% 
  • Alternative treatment for patients with clinical ASCVD with contraindications against high-intensity statins or with side effects from statin therapy
  • For ≥75-year-old patients with ASCVD with contraindications/intolerance to high-intensity statins
  • For 40-75-year-old patients with diabetes mellitus with or without 5-≤7.5% 10-year ASCVD risk
  • For 40-75-year-old patients with diabetes mellitus and LDL-C 70-189 mg/dL
  • For 40-75-year-old patients with diabetes mellitus or LDL-C ≥190 mg/dL with contraindications/intolerance to high-intensity statins
  • For 40-75-year-old patients without diabetes mellitus but LDL-C ≥70 mg/dL and ≥7.5% 10-year ASCVD risk

• Low-intensity statins: Simvastatin (10 mg), Pravastatin (10-20 mg), Lovastatin (20 mg), Fluvastatin (20-40 mg)
  • Daily dose helps lower LDL-C by <30%
• Treatment with statin is associated with the risk of developing statin-associated muscle symptoms (SAMS) or new-onset DM but benefits of statin therapy for CV risk reduction outweigh the risk
• A non-statin drug may be added to a maximally tolerated statin therapy if LDL-C goal based on CVD risk has not been achieved

¹Risk of developing a first ASCVD event, defined as nonfatal myocardial infarction or coronary heart disease (CHD) death or fatal or nonfatal stroke, over a 10-year period among people free from ASCVD at the beginning of the period.

Selective Cholesterol-Absorption Inhibitor

• Eg Ezetimibe
• Used as an adjunct to diet and exercise for the reduction of elevated TC, LDL-C, apo B and non-HDL-C in patients with primary hyperlipidemia alone or in combination with statin therapy, or in combination with Fenofibrate in patients with mixed hyperlipidemia
• 1st optional non-statin to consider for patients with poor tolerance to statins
• 1st option to add onto maximally tolerated statin therapy in patients who are less responsive to statins and failed to reach LDL-C goals
  • May be added to a maximally tolerated statin therapy in patients with high to very high-risk clinical ASCVD when LDL-C level remains ≥70 mg/dL
  • Combination is a strategy to prevent side effects associated with statin monotherapy
  • Combination products of selective cholesterol-absorption inhibitor + statin, eg Ezetimibe/Simvastatin, Ezetimibe/Atorvastatin, are available and may be used to reduce TC, LDL-C, apo B, TG and non-HDL-C and to increase HDL-C in patients with homozygous familial hypercholesterolemia
    • The IMPROVE-IT trial in patients with recent acute coronary syndrome showed further decrease in LDL-C and reduction in cardiovascular events with the addition of Ezetimibe to a moderate-intensity statin (Simvastatin) over 6 years of follow-up
    • The SHARP trial demonstrated reductions in LDL-C and primary endpoint of 1st major ASCVD event with Ezetimibe plus Simvastatin when compared to placebo over 4.9 years of follow-up
  • If the addition of Ezetimibe to a statin achieved therapy goals, the combination therapy may be continued with continuous monitoring of treatment response
• Ezetimibe/statin combination is recommended in patients with CKD stage 3-5 not dependent on dialysis
• Selective potent inhibitor of cholesterol absorption in the intestinal lumen and reduces the overall delivery of cholesterol to the liver
• Causes moderate reduction in LDL-C levels
  • When used alone, Ezetimibe decreases LDL by 10-20% with favorable effects on HDL and TG
  • When used in combination with statins, there is an additional reduction in LDL-C by 18-25% with favorable effects on HDL and TG, with Fenofibrate 20-22% reduction in LDL-C

Proprotein Convertase Subtilisin/Kexin Type 9 Monoclonal Antibodies (PCSK9 mAbs) 

• Eg Alirocumab, Evolocumab
• May be given alone or in combination with other lipid-lowering therapies as an adjunct to diet to reduce LDL-C in patients with primary hyperlipidemia including heterozygous familial hypercholesterolemia
• Recommended as adjunct to diet and maximally tolerated statin therapy plus Ezetimibe for the treatment of homozygous familial hypercholesterolemia with very high-risk clinical ASCVD that needs further reduction of LDL-C
• Addition of a PCSK9 mAb is recommended to patients with high-risk clinical ASCVD or severe primary hypercholesterolemia with multiple risk factors for ASCVD events if the LDL-C level remains above goal on maximally tolerated statin and Ezetimibe therapy
• Given also to patients with high and very high CV risk with intolerance to statin therapy  
• May be preferred as the initial non-statin agent in addition to maximally tolerated statin therapy in patients with clinical ASCVD at very high risk that still require ≥25% LDL-C reduction  
• As human monoclonal PCSK9 antibody, it binds to PCSK9 which then increases LDL receptor density to aid in clearing circulating LDL-C 
• Lowers LDL-C levels by 48-71%, TC by 36-42%, apo B by 42-55%, and non-HDL-C by 49-58%

Anti-sense Apoliporotein B Oligonucleotides 

• Eg Mipomersen
• May be used for patients with homozygous familial hypercholesterolemia unresponsive to PCSK9 mAb therapy; may also be considered in patients with ASCVD and baseline LDL-C ≥190 mg/dL who had inadequate response to statin therapy (with or without Ezetimibe and PCSK9 mAbs)
• Hybridization to mRNA results to RNase H-mediated degradation of mRNA used for translation of apo B-100
• Lowers LDL-C levels by 21%, total cholesterol by 19%, apo B by 24%, and non-HDL-C by 22%

Bempedoic Acid

• Indicated for the treatment of adults with heterozygous familial hypercholesterolemia or established ASCVD who require additional lowering of LDL-C 
• Addition of Bempedoic acid may be considered if additional LDL-C lowering is needed in patients with clinical ASCVD at high or very high risk despite treatment with a maximally tolerated statin therapy with Ezetimibe and/or a PCSK9 mAb
• Lowers LDL-C by inhibiting action of adenosine triphosphate-citrate lyase, which is an enzyme that works upstream of HMG-CoA reductase
• May be used alone or in fixed combination with Ezetimibe
  • Has been shown to decrease LDL-C by 15-24% and in combination with Ezetimibe by 36% in clinical trials

Bile Acid Sequestrants

• Eg Cholestyramine, Colesevelam, Colestipol  
• Adjunct to diet for LDL-C reduction in patients with primary hyperlipidemia
• Have been shown to reduce risk for CVD; considered in patients who have contraindications or intolerance to statin therapy
• Also effective in LDL lowering in patients with diabetes mellitus
• Bind bile acids in the intestine through anion exchange and impede their reabsorption 
• Cause moderate reduction in LDL-C levels
  
  • LDL-lowering potential increases when combined with other agents (eg statins)
  • May raise TG levels in some patients
  • Decrease LDL-C by 15-25%; increase HDL-C by 4-11%

Evinacumab   

• An add-on treatment for patients ≥12 years old with homozygous familial hypercholesterolemia 
• May also be considered in patients without clinical ASCVD or with clinical ASCVD at very high risk and baseline LDL-C ≥190 mg/dL not from secondary causes who had inadequate response to maximal doses of statin with Ezetimibe and/or a PCSK9 mAb, Bempedoic acid or Inclisiran
• A fully human monoclonal antibody that binds to angiopoietin-like protein 3 (ANGPTL₃) which in turn inhibits lipoprotein and endothelial lipase 
• Mean LDL-C reduction in combination with other lipid-lowering therapies has been shown to be 49%

Inclisiran   

• Indicated for the treatment of adults with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidemia, or clinical ASCVD requiring additional lowering of LDL-C   
• Given as an adjunct to diet in combination with a statin or statin with other lipid-lowering therapies in patients unable to reach LDL-C goals with max tolerated statin dose; or alone or in combination with other lipid-lowering therapies in patients who are statin intolerant or for whom a statin is contraindicated 
• May be used in place of a PCSK9 mAb in patients with poor adherence to PCSK9 mAbs, adverse effects from both PCSK9 mAbs, or those who may be not be able to self-inject
• It is a small-interfering RNA LDL-C-lowering treatment that targets hepatic PCSK9 synthesis which prolongs LDL receptor activity 
• Dosing regimen is infrequent (initial dose is given subcutaneously which is repeated at 3 months then every 6 months) and side effects are acceptable
• Mean LDL-C reduction has been shown to be 48-52% 

Microsomal Triglyceride Transfer Protein (MTP) Inhibitor

• Eg Lomitapide
• Used for patients with homozygous familial hypercholesterolemia as an adjunct to a low-fat diet and other lipid-lowering treatments including LDL apheresis  
• May also be considered in patients without clinical ASCVD or with clinical ASCVD at very high risk and baseline LDL-C ≥190 mg/dL not from secondary causes who had inadequate response to maximally tolerated statin therapy with Ezetimibe and/or PCSK9 mAb, Bempedoic acid or Inclisiran  
• Inhibits chylomicron and VLDL synthesis by direct binding and inhibition of MTP
• Lowers LDL-C levels by 40%, TC by 36%, apo B by 39%, TG by 45%, and non-HDL-C by 40%

Nicotinic Acid

• Favorably affects all lipid and lipoproteins when given in the proper dosage
  
  • Lower doses increase HDL-C
  • 2-3 g/day are needed to lower LDL-C
• Moderate reduction in CVD risk
• Alter lipid levels by inhibiting lipoprotein synthesis and decreasing the production of VLDL particles by the liver
• Most effective at raising HDL levels among lipid-modifying drugs
  
  • Decrease LDL-C by 5-25%
  • Increase HDL-C by 10-35%
  • Decrease TG by 20-30% in a dose-dependent manner
• May be combined with statins in managing DM patients with hypertriglyceridemia
• May increase blood glucose levels

Intensified LDL-C-Lowering Pharmacotherapy

• Dose increase; escalate intensity of statin therapy
• Combination therapy eg statin with Ezetimibe with or without a PCSK9 mAb, statin with PCSK9 mAb, Ezetimibe with PCSK9 mAb, statin with bile acid sequestrant
• LDL apheresis may be considered in patients with familial hypercholesterolemia unresponsive to dietary management and pharmacological therapy

Triglyceride-Lowering and HDL-C-Raising Pharmacological Therapy

Fibrates

• Primary use is for lowering TG
  • Decrease TG by 20-50%
  • May be combined with statins in managing diabetes mellitus patients with hypertriglyceridemia and low HDL-C
  • If TG is not elevated, fibrates may lower LDL-C by 5-20%
• Also useful in combined/mixed dyslipidemia and in increasing HDL-C by 6-35%
• Recommended for patients with very high TG (>4.5 mmol/L) who are at risk for pancreatitis
• Moderately reduce risk for CHD
• Favorably lower LDL in patients with diabetes mellitus
• Down-regulate the apolipoprotein C-III (apoC-III) gene and up-regulate genes for apolipoprotein A-1, fatty acid transport protein, fatty acid oxidation and possibly lipoprotein lipase
• Primarily target atherogenic dyslipidemia including diabetic dyslipidemia
  
  • Fenofibrate with or without statin therapy reduces progression of diabetic retinopathy
• When used in combination with LDL-lowering drugs, it improved the overall lipoprotein compared to either agent alone
  • In combination with statin, Fenofibrate is the preferred fibrate to use due to lower risk of myopathy and rhabdomyolysis
• Provide an alternative treatment in statin-intolerant patients with mild to moderate hypercholesterolemia
• In patients in whom a fibrate is recommended, Nicotinic acid can also be considered
• Pemafibrate is a novel selective peroxisome proliferator-activated receptor alpha (PPARα) modulator with a favorable benefit-risk balance compared to conventional fibrates 
  • May be used to treat patients with hypertriglyceridemia and to prevent CV events in those with hypertriglyceridemia

Nicotinic Acid

• Please see discussion under LDL-C-Lowering Pharmacological Therapy

Omega-3 Fatty Acids

• Total eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at dosages between 2 to 4 g/day can lower serum TG levels 
  • Studies showed EPA reduced serum TG levels by up to 45% in a dose-dependent manner 
• Icosapent ethyl (IPE) is a highly purified, non-oxidized form of EPA and is indicated for patients with TG levels ≥150 mg/dL with established ASCVD or diabetes with ≥2 ASCVD risk factors and on maximally tolerated statins to prevent ASCVD morbidity and mortality

Volanesorsen  

• Clinical trials have shown its efficacy in the treatment of patients with elevated TG and familial chylomicronemia syndrome (FCS) 
  • Given to adult patients with FCS and at high risk for pancreatitis with inadequate response to a low-fat diet and TG-lowering therapy 
• An antisense oligonucleotide that binds to apoC-III mRNA and prevents translation of apoC-III allowing for the metabolism and breakdown of TG and chylomicrons

Treatment of Specific Dyslipidemias

Very High LDL Cholesterol (≥4.9 mmol/L [≥190 mg/dL])

• Usually caused by genetic forms of hypercholesterolemia
• For patients at very high risk and with persistent high risk, use a maximally tolerated statin and, if necessary, Ezetimibe to lower LDL-C levels; if still not at treatment goal, a PCSK9 mAb may be added 
• May consider addition of a bile acid sequestrant in patients 20-75 years old with an LDL-C level of ≥4.9 mmol/L (≥190 mg/dL) with <50% reduction in LDL-C and TG ≤3.4 mmol/L (≤300 mg/dL) while on maximally tolerated statin and Ezetimibe therapy

Elevated Triglycerides

• Strong association between high TG levels and CHD risk
• TG levels ≥2.3 mmol/L (≥200 mg/dL) indicate the need to identify non-HDL-C level, which is the secondary target of lipid-lowering therapy in these patients (LDL-C is still the primary goal of therapy)
  
  • Non-HDL-C is more representative of all atherogenic lipoproteins than LDL-C
    • Non-HDL-C (mmol/L) = TC-HDL-C; non-HDL-C levels can be calculated from non-fasting serum

• Acquired causes: Obesity, physical inactivity, excess alcohol intake, high carbohydrate diet
  
  • Secondary causes (eg diabetes mellitus, chronic renal failure, nephrotic syndrome, chronic liver disease, hypothyroidism, Cushing’s disease, various medications, etc)
  • Genetic causes

• Elevated TG can often be effectively treated through lifestyle changes; however, fibrates, Niacin, and combination therapy with statins may be appropriate options for many patients

• Very high TG (>5.6 mmol/L [≥500 mg/dL])
  • Treatment should be likened to an emergency to avoid acute pancreatitis
    • Fibrate (preferably Fenofibrate), prescription omega-3 fatty acids, or Nicotinic acid should be started
  • Lifestyle modifications
    • Fish oils can replace some long-chain TG in diet

• If LDL-C is still elevated despite a fibrate, consider adding a statin
  
  • Decision must be individualized
  • Must be started only when it is strongly indicated
  • The recommended fibrate to be combined with a statin is Fenofibrate

• High TG (2.3-5.6 mmol/L [200-499 mg/dL])
  
  • Lifestyle modifications
  • If LDL-C or non-HDL-C levels are high or ASCVD risk ≥5%: Start statin
    • Consider combination therapy with Fenofibrate if LDL-C is at goal but TG level remains >200 mg/dL in primary prevention or high-risk patients 
    • Consider combination therapy with Icosapent ethyl if TG level is between 135-499 mg/dL despite statin therapy in patients at high risk (or above) 

• Borderline high TG (1.7-2.2 mmol/L [150-199 mg/dL])
  
  • Lifestyle modifications
  • Medications are rarely required unless LDL-C is elevated above target level

Low HDL-C (1 mmol/L [<40 mg/dL])

• Low HDL-C is a strong, independent predictor of CHD
• Excluding secondary causes of low HDL-C and in the presence of other risk factors (eg borderline LDL-C, personal history of CAD, or a family history of premature CAD, HDL-C levels should be raised by as much as possible to levels of at least >40 mg/dL in both men and women
• Raising HDL-C levels alone in patients without accompanying risk factors is not recommended

Low HDL-C without Hypertriglyceridemia

• Causes: Obesity, physical inactivity, cigarette smoking, type 2 DM, certain drugs, etc
• Treatment in patients with CHD or CHD-risk equivalents when lifestyle modifications fail to increase HDL include fibrates or Nicotinic acid

Low HDL-C with Hypertriglyceridemia

• HDL-C is low and TG is high and LDL-C is not significantly elevated: Start fibrates or Nicotinic acid

Elevated Lipoprotein(a)

• Aggressive reduction of LDL-C will help lower Lp(a)
• Agents that have shown to reduce Lp(a) by approximately 20-30% include high-dose Niacin, PCSK9 mAbs, Estrogen and Aspirin
  • Niacin reduces Lp(a) by an average of 25% and may be given to patients with elevated Lp(a) and hypercholesterolemia with elevated LDL-C despite maximum tolerated statin therapy and Ezetimibe

Atherogenic Dyslipidemia (Triglycerides ≥1.7 mmol/L [≥150 mg/dL] and HDL-C <1 mmol/L [<40 mg/dL])

• The patient likely has metabolic syndrome
• Attempt adequate trial of lifestyle modification to meet LDL-C goals
  
  • Add LDL-lowering drug therapy if lifestyle modification fails to reach LDL-C goals

• TG <2.3 mmol/L (<200 mg/dL): Drug therapy to lower TG is not necessary
  
  • If patient has CHD or CHD-risk equivalents, consider using drug therapy to raise HDL-C (eg fibrates or Nicotinic acid) 

• TG 2.3-5.7 mmol/L (200-499 mg/dL): If non-HDL-C remains elevated after adequate LDL-C-lowering therapy: May consider higher dose of statin or statin + TG-lowering drug (fibrate or Nicotinic acid)

Apolipoproteins

• Target apo B level at <90 mg/dL for patients at risk of CAD, including those with diabetes mellitus 
• Target apo B level at <80 mg/dL for patients with established CAD or DM plus ≥1 additional risk factor

Familial Hypercholesterolemia 

• Common autosomal dominant genetic disease that causes LDL-C level elevation
• Causes early-onset CHD
• Dutch Lipid Clinic Network criteria are used for the diagnosis of heterozygous familial hypercholesterolaemia in adults and include the following:
  • Family history
    • 1st-degree relative with known premature* coronary or vascular disease, or 1st-degree relative with known LDL-C >95th percentile = 1 point
    • 1st-degree relative with tendinous xanthomata and/or arcus cornealis, or children <18 years old with LDL-C >95th percentile = 2 points
  • Clinical history 
    • Premature* coronary artery disease = 2 points
    • Premature* cerebral or peripheral vascular disease = 1 point
  • Physical examination
    • Presence of tendinous xanthomata = 6 points
    • Presence of arcus cornealis before 45 years old = 4 points
  • LDL-C levels (without treatment)
    • LDL-C ≥8.5 mmol/L (≥325 mg/dL) = 8 points
    • LDL-C 6.5-8.4 mmol/L (251-325 mg/dL) = 5 points
    • LDL-C 5.0-6.4 mmol/L (191-250 mg/dL) = 3 points
    • LDL-C 4.0-4.9 mmol/L (155-190 mg/dL) = 1 point
  • DNA analysis
    • Functional mutation in the LDLR, apoB, or PCSK9 genes = 8 points
  • Definite diagnosis of familial hypercholesterolemia can be made if the score is >8 points, probable if 6-8 points, possible if 3-5 points
• Treatment of familial hypercholesterolemia includes the following:
  • Lifestyle modification that includes intervention on smoking, diet and physical activity
  • Initiation of cholesterol-lowering drugs that include statins (maximal potent dose), Ezetimibe, PCSK9 mAbs (Alirocumab, Evolocumab), bile acid-binding resins, Bempedoic acid or Evinacumab

*Premature = <55 years old in men, <60 years old in women

Pediatric Dyslipidemia

• Benefits of developing healthy lifestyle habits in children have been recognized
• Recommended first-line approach is intensive lifestyle modifications (with emphasis on improved dietary intake and normalization of body weight)
  
  • It is recommended that lifestyle changes in children should be implemented for at least 6-12 months prior to considering pharmacologic therapy
• Studies have shown that high-fiber, low-fat diets are also beneficial in children by helping reduce cholesterol levels
  • However, monitoring of fat-soluble vitamin status in children on low-fat diet is recommended since this may reduce absorption of these vitamins
• Avoid high carbohydrate diet in children with hypertriglyceridemia
• Smoking cessation should also be implemented
• Fish oil supplements are considered to have significant effects on TG levels in children, especially in those with end-stage renal insufficiency
• Dietary supplementation with plant stanols and sterols (eg orange juice, yogurt drinks, cereal bars, margarines/ spreads, dietary supplements) may be considered for children with severe hypercholesterolemia or those who are at high risk
  
  • Above supplements may also reduce absorption of fat-soluble vitamins; monitoring of fat-soluble vitamin status is also recommended
• Pharmacotherapy is generally reserved for those with severe dyslipidemia or those with genetic lipid disorders
• Other candidates for pharmacotherapy include children and adolescents >8 years of age who satisfy the following criteria:
  
  • LDL-C level of ≥190 mg/dL or
  • LDL-C level of ≥160 mg/dL plus
    • Presence of ≥2 CAD risk factors
    • Family history of premature CAD (<55 years of age)
    • Being overweight or obese, or having other elements of insulin resistance syndrome
  • Pediatric diabetic patients with LDL level of ≥130 mg/dL

• Pharmacotherapeutic options for pediatric dyslipidemia include the following:
  
  • Based on available evidence, statins are considered safe and effective 
    • Statin therapy can be initiated at 6-10 years of age for the treatment of children with familial hypercholesterolemia in addition to healthy lifestyle measures
  • Pediatric studies have demonstrated 15-20% reductions in LDL-C level with bile acid sequestrants
    • Cholestyramine is currently approved for hypercholesterolemia in children and should be initiated at <8 g daily
    • Safety and efficacy of Colestipol and Colesevelam have not yet been established in pediatric patients although Colestipol may be started at <10 g daily while Colesevelam is approved for children ≥8 years of age
    • Bile acid sequestrants may lead to folic acid and cholecalciferol depletion; multivitamins should therefore be used
    • Bile acid sequestrants should not be used in children with hypertriglyceridemia
  • Fibrates may be useful in children with severe hypertriglyceridemia and at increased risk of pancreatitis
    • Use of fibrates in children or adolescents with type I or V hyperlipoproteinemia warrants close monitoring
  • Ezetimibe may be used in children ≥10 years of age and adolescents with homozygous familial hypercholesterolemia or sitosterolemia
  • Evolocumab is used as an adjunct to diet and other LDL-C-lowering therapies in children ≥10 years of age and adolescents with heterozygous familial hypercholesterolemia
  • Experience with Niacin therapy in children is limited

COVID-19 and Lipid-lowering Therapy

• Current evidence shows that lipid-lowering therapy is safe in patients with COVID-19 infection 
  • Lipid-lowering therapy should be continued in patients with confirmed COVID-19 diagnosis and abnormal liver function tests (LFTs) unless alanine transaminase (ALT) or aspartate transaminase (AST) progressively increases, a significant drug-drug interaction between the lipid-lowering agents and COVID-19 drugs has been identified, or patient is critically ill and/or cannot take oral medications