Hyperlipidemia Flashcards

1
Q

What’s normal Total Cholesterol value?

A

<200 mg/dL

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2
Q

Normal LDL-C ?

A

<100 mg/dL

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3
Q

What’s a low HDL-C value in men and women ?

A

Men : < 40 mg/dL
Women : <50 mg/dL

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4
Q

What are normal TG levels?

A

<150 mg/dL

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5
Q

Risk factors for Atherosclerosis :

What’s the primary cause of atherosclerosis?

Name some MAJOR risk factors

A

LDL-C

Cigarette smoking, HTN, Diabetes, Other lipoprotein abnormalities, risk incr with age, race/ethnicity , family history of premature CHD

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6
Q

Biomarkers associated with ASCVD Risk? State the value associated with each

Apo B
Lp(a)
Non-HDL (TC-HDL)
hsCRP

A
  1. > =130 mg/dL
  2. > = 50 mg/dL
  3. > = 190 mg/dL
  4. > = 2 mg/dL
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7
Q

WHat’s the non pharm therapy ?

A

Aerobic exercise for >= 150 mins/week or 30 mins/day most of the week

for weight loss : 200-300 mins per week

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8
Q

Non pharm Therapy : Diet

Name some dietary changes pt’s can make

A
  1. fruits /veggies
  2. whole grains
  3. healthy sources of protein : protein from plants, fish and seafood, low fat dairy products , avoid processed forms of meat/poultry
  4. liquid plant oils rather than tropical oils or animal fats
  5. Choose minimally processed foods
  6. minimize intake of foods with added sugars
  7. Choose and prepare foods with little or no salt
  8. limit intake of alcohol
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9
Q

First statin benefit Group - Clinical ASCVD

Name some major ASCVD Events that would land a pt in this category

Name some high risk conditions

A

A. recent acute coronary syndrome (within 12 months)
-history of MI
-history of Ischemic stroke,
-symptomatic peripheral arterial disease

B. Age >= 65 yrs,
-heterozyg familial hypercholesterolemia
-hx prior coronary artery bypass surg or percutaneous coronary intervention outside of the major ASCVD events
-Diabetes
-HTN
-CKD
-currently smoking
-persistently elevated LDL-C greater than 100 despite max tolerated statin therapy and Zetia
-history congestive HF

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10
Q

Whats the Statins cholesterol reduction efficacy for LDL, non-HDL, TG, and HDL?

A

LDL : decr 18-55%
Non HDL : decr 15-51%
TG : decr 7-30%
HDL : Incr 5-15 %

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11
Q

When should you monitor LDL-C after taking statins?

A

Fasting lipids 4-12 weeks after statin or non statin therapy initiation or dose adjustment AND THEN every 3-12 months thereafter

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12
Q

Major AE’s for statins? (3)

A
  1. Statin associated muscle sx’s (SAMS) –> Myopathies, myalgias, rhabdo . Monitor CK only as indicated
  2. elevated hepatic transminases (primarily ALT) -> Monitor AST/ALT at baseline then as indicated
  3. New onset diabetes
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13
Q

Statins : CI? (3)

Simvastatin 80 mg should only be continued in pt’s who?

Avoid large quantities of ____

A

-Active/acute liver disease (Chronic disease ok)
-Pregnancy
-breastfeeding

Have tolerated that dose for >12 months (no new starts)

Grapefruit juice >1 quart daily

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14
Q
  1. What’s CI with simvastatin?
  2. DONT exceed 10 mg simvastatin daily with? (2)
  3. DONT exceed 20 mg simvastatin daily with?(3)
A

Itra, keto, posa - conazole

Erythro, clarithro, telithro -mycin

HIV protease inhibs

nefazodone, gemfibrozil, cyclosporine, danazol

  1. Verapamil, diltiazem
  2. Amiodarone, amlodipine, ranolazine
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15
Q

Cholesterol Absorption Inhibitors (ezetimibe)

Cholesterol reduction efficacy? LDL ?

Major AE?

Dose?

A
  1. Lowers LDL 10-18% as monotherapy, Lowers LDL 34-61% with statins
  2. Diarrhea
  3. 10 mg PO daily w/or without food
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16
Q

PCSK9 Inhibitors : MOA

A

Human mAB that binds to PCSK9 inhibiting the degradation of the LDL receptor in lysosome. LDL r’s can be recycled to cell surface and continue to clear LDL-C

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17
Q

PCSK9 Inhibitors :

Cholesterol Reduction Efficacy?

AE’s ? (4)

No evidence of?

Dose for both drugs

A

LDL decr up to 60% in statin tx patients

Injection site rxn, flu like sx’s, URTI, nasopharyngitis

Incr in cognitive ae’s

Alirocumab (Praluent) : 75 mg sc q2weeks, if LDL-C reduction bad after 4-8 wks, may incr to 150 mg SC q2wks

Evolocumab (Repatha) : 140 mg q2weeks, if LDL reduction bad after 12 wks, incr dose to 420 mg every 2 wks OR you can do 420 mg SC monthly

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18
Q

Bile Acid Sequestrants : Colesevelam, Colestipol, Cholestyramine

MOA?

A

Not systemically absorbed ! Binds BA in intestine and impedes their reabsorption. By decr the bile acid pool, liver increases conversion of cholesterol to bile acids

19
Q

Bile Acid Sequestrants : Cholesterol reduction efficacy?

A

LDL : decr by 15-26%
TG : MAY INCR!! avoid in TG levels exceeding 300 mg/dL
A1C : Decr by 0.5%

20
Q

BA sequestrants : AE’s ? (5)

Which forms are better tolerated?

DDI’s?
-impaired abs of?
-Reduced Bioavail of?
-Avoid DDI’s by??

A

AE’s : Difficult to tolerate (constipation, bloating, epigrastric fullness, nausea, flatulence)

tablet forms

-impaired abs of fat soluble vits ADEK
-reduced Bioavail of warfarin, levo, phenytoin
-avoid DDI’s by taking 1 hour before or 4 hrs after BAS

21
Q

BA sequestrants : CI? (2)

What are the pros?

A

bowel obstruction
Hx of hypertriglyceridemia-induced pancreatitis

It can lower A1c and its safe in pregnancy

22
Q

Dosing for the following :

  1. Colesevelam (Welchol)
  2. Cholestyramine (questran)
  3. Colestipol (Colestid)
A
  1. 6 tabs po daily or 3 tabs po BID (with meal and liquid) –> 625 mg tablet form

suspension : take one 3.75 G packet po daily or 1.875 g packet po twice daily (Mix with 8 ounces of water, or fruit juice, and take with meal)

  1. 8-16 grams po daily, divided into 2 doses
  2. 2-16 g po daily in 1-2 divided doses
23
Q

Third Statin Benefit Group - Diabetes

  1. What are some ASCVD risk enhancers? (6)
  2. Lipid biomarkers?
  3. In select individuals if measured : Hs-CRP , LP(a), ApoB, ABI
  4. Kim, see chart for diabetes protocol !
A
  1. fam hx premature ASCVD
    -persistent elevated LDL-C>= 160 mg/dL
    -CKD
    -metabolic syndrome
    -conditions specific to women (preeclampsia, premature menopause)
    -inflamm diseases (RA, psoriasis, HIV)
    -Ethnicity (south asian ancestry)
  2. persistently elevated triglycerides (>175 mg/mL)
  3. > 2 mg/L,
    LP(a) > 50 mg/dL
    ApoB >= 130 mg/dL
    ABI < 0.9 (bad)
24
Q

New LDL-C Lowering Pharm Therapies : Inclisiran

MOA?

A

Small interfering RNA (siRNA) molecule that reduces the production of pcsk9 by inhibiting mRNA

25
Q

Inclisiran :

Cholesterol reduction efficacy?

AE’s? (2)

Dose?

A

LDL decr average of 50% in statin tx patients

Injection site rxns (transient and mild) + Bronchitis

284 mg SQ once, again at 3 months and then 6 months thereafer

26
Q

ACL (Adenosine triphos citrate lyase) inhibitors (Bempedoic Acid)

MOA?

A

Inhibs ACL which lowers LDL-C by inhibition of cholesterol synthesis upstream of HMG-CoA

27
Q

ACL Inhibs (Bempedoic Acid)
1. Lowers LDL by how much in combo with statin?
2. In combo with Zetia AND statin?

AE’s ? (6)

A
  1. 17-18%
  2. 38%

URTI,
muscle spasms
hyperuricemia
back pain
abdominal pain/discomfort, elevated liver enzymes

28
Q

ACL Inhibs : Dosing

  1. Bempedoic acid (Nexletol)
  2. Bempedoic acid/ezetimibe (Nexlizet)
A
  1. 180 mg po daily w/or without food
  2. 180 mg/10 mg po daily with or without food
29
Q

HDL Targeter : Niacin

What is the MOA?

A

inhibs hormone sensitive lipase leading to a decrease in free fatty acids in plasma and decr hepatic synthesis of TG’s. Signif raises HDL-C reducing its catabolism and selectively decr hepatic removal of HDL

30
Q

Niacin and how it affects the following :
TG, LDL-C, HDL-C

Major AE’s? (4)

A

TG decr 20-50% (Good)
LDL-C Decr 5-20%
HDL-C INCR 5-30% !!

-Prostaglandin mediated cutaneous flushing (IR>ER)
-Hepatotoxic
-decr uric acid secretion –> Hyperuricemia
-can incr insulin resistance

31
Q

AIM-HIGH Trial Niacin

Despite incr in HDL-C and favorable effects on lipid profile, what was not noted?

A

NO CV benefit seen!

32
Q

Omega 3 Fatty Acids (DHA + EPA)

How does it effect the following? TG, TC, VLDL, HDL, LDL

A

TG : Decr 27-45%

TC : Decr 7-10%

VLDL : Decr 20-42%

HDL : Incr 8-14%

LDL : Incr is variable

33
Q

Omega 3 Fatty Acids (DHA + EPA)

Major AE’s ? (5)

Dosing for Lovaza (Omega 3 acid ethyl esters) and Vascepa (Icosapent ethyl) ?

A

Diarrhea, GI uspet, N/V, Fishy breath, may incr risk of bleeding

Lovaza : 4 g once daily or 2 g twice daily

Vascepa : 2 g twice daily

34
Q

Fibrates : Gemfibrozil and Fenofibrate

MOA?

A

Incr LPL activity and reduces Apo C-III by activating PPARalpha receptor which regulates the expression of genes involved in regulation of lipids

in turn, this decr free fatty acids and decr triglyceride rich VLDL

35
Q

Fibrates : how does it affect the following
TG, HDL-C, LDL-C and TC ?

What are the ae’s ? (3) (GGM)

A

TG : Decr 20-25% (Good!)
HDL : Incr 10-15%
LDL and TC : Decr 20-50%

  1. GI upset
  2. May enhance formation of gallstones
  3. Myopathies (especially with gemfibrozil when used with statins - fenofibrate preferred w/statin use)
36
Q

Gemfibrozil (LOPID) Dose?

Fenofibrate (Tricor) Dose?

what have clinical trials found?

A
  1. 600 mg BID 30 mins before breakfast and dinner
  2. depends on formulation
  3. They reduce coronary events as monotherapy but NOT when used in combo with statins
37
Q

Familial Hypercholesterolemia : Management for

  1. HeFH ? (LDLC >190 mg/dL w/similar first degree relative)
  2. HoFH? (LDLC>400 mg/dL and 1 or both parents with Dx)
A
  1. high intens statins, PCSK9I, bempedoic acid
  2. Lipoprotein apheresis, evinacumab, lomitapide, evolocumab , statins reduce LDLc modestly even in those who are receptor negative
38
Q

Evinacumab :

  1. MOA?
  2. LDLC, TC, ApoB, Non HDL, HDL?
  3. AE”s? (5)
  4. What has NOT been determined?
A
  1. hmAB binds and inhibs ANGPTL3. this is expressed in liver and involved in lipid metab by inhibiting LPL and EL.
  2. LDL decr by 49%, TC decr 48%, Apo B decr 37%, Non HDL Decr 52%, HDL Decr 30%
  3. Nasopharyngitis, rhinorrhea, influenza like illness, dizziness, nausea
  4. cardiovasc benefit
39
Q

MTP Inhib (Lomitapide)

MOA?

LDLC, TC, ApoB, Non HDL?

Major ae’s?

what has not been determined?

A
  1. inhibs MTP, preventing assembly of apo B containing lipoproteins in enterocytes and hepatocytes (inhibits synthesis of chylomicrons and VLDL)
  2. LDL decr 40%, TC decr 30%, ApoB decr 39%, Non-HDL decr 40%
  3. Liver toxic. (incr ast/alt/alk phos/T bili); hepatic steatosis (BBW and REMS requirement)
    -diarrhea, N/V/abd pain, vitamin deficiency
  4. Cardiovasc benefit
40
Q

Elderly Age > 75

  1. If already on statin what do u do?
  2. May be at higher risk for? SO do what?
A
  1. continue if tolerated
  2. Statin intolerance, initiate moderate intensity statin if necessary
41
Q

Special Pop : Pregnant

  1. What’s safe?
  2. FDA removed CI for use of statins during pregnancy .
    -Discuss some of the risk versus benefit situations (2)
A
  1. BA sequestrants
  2. Consider CONTINUING statin for those with clinical ASCVD , or HoFH
  • COnsider HYDROPHILIC statin (Pravastatin) over lipophilic statin
42
Q

PT’s with CKD not on Hemodialysis

  1. Have higher risk of ?
  2. Still benefit from ?

PT’s with CKD ON HEMODIALYSIS

  1. Benefit???
A
  1. ASCVD
  2. Statin use for primary prevention
  3. no signif benefit in vascular outcomes! Initiation is NOT recommended
43
Q

Kim, See Chart for 4th statin benefit group

A

Primary prevention