Hyperlipidemia Flashcards
What’s normal Total Cholesterol value?
<200 mg/dL
Normal LDL-C ?
<100 mg/dL
What’s a low HDL-C value in men and women ?
Men : < 40 mg/dL
Women : <50 mg/dL
What are normal TG levels?
<150 mg/dL
Risk factors for Atherosclerosis :
What’s the primary cause of atherosclerosis?
Name some MAJOR risk factors
LDL-C
Cigarette smoking, HTN, Diabetes, Other lipoprotein abnormalities, risk incr with age, race/ethnicity , family history of premature CHD
Biomarkers associated with ASCVD Risk? State the value associated with each
Apo B
Lp(a)
Non-HDL (TC-HDL)
hsCRP
- > =130 mg/dL
- > = 50 mg/dL
- > = 190 mg/dL
- > = 2 mg/dL
WHat’s the non pharm therapy ?
Aerobic exercise for >= 150 mins/week or 30 mins/day most of the week
for weight loss : 200-300 mins per week
Non pharm Therapy : Diet
Name some dietary changes pt’s can make
- fruits /veggies
- whole grains
- healthy sources of protein : protein from plants, fish and seafood, low fat dairy products , avoid processed forms of meat/poultry
- liquid plant oils rather than tropical oils or animal fats
- Choose minimally processed foods
- minimize intake of foods with added sugars
- Choose and prepare foods with little or no salt
- limit intake of alcohol
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. 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
Whats the Statins cholesterol reduction efficacy for LDL, non-HDL, TG, and HDL?
LDL : decr 18-55%
Non HDL : decr 15-51%
TG : decr 7-30%
HDL : Incr 5-15 %
When should you monitor LDL-C after taking statins?
Fasting lipids 4-12 weeks after statin or non statin therapy initiation or dose adjustment AND THEN every 3-12 months thereafter
Major AE’s for statins? (3)
- Statin associated muscle sx’s (SAMS) –> Myopathies, myalgias, rhabdo . Monitor CK only as indicated
- elevated hepatic transminases (primarily ALT) -> Monitor AST/ALT at baseline then as indicated
- New onset diabetes
Statins : CI? (3)
Simvastatin 80 mg should only be continued in pt’s who?
Avoid large quantities of ____
-Active/acute liver disease (Chronic disease ok)
-Pregnancy
-breastfeeding
Have tolerated that dose for >12 months (no new starts)
Grapefruit juice >1 quart daily
- What’s CI with simvastatin?
- DONT exceed 10 mg simvastatin daily with? (2)
- DONT exceed 20 mg simvastatin daily with?(3)
Itra, keto, posa - conazole
Erythro, clarithro, telithro -mycin
HIV protease inhibs
nefazodone, gemfibrozil, cyclosporine, danazol
- Verapamil, diltiazem
- Amiodarone, amlodipine, ranolazine
Cholesterol Absorption Inhibitors (ezetimibe)
Cholesterol reduction efficacy? LDL ?
Major AE?
Dose?
- Lowers LDL 10-18% as monotherapy, Lowers LDL 34-61% with statins
- Diarrhea
- 10 mg PO daily w/or without food
PCSK9 Inhibitors : MOA
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
PCSK9 Inhibitors :
Cholesterol Reduction Efficacy?
AE’s ? (4)
No evidence of?
Dose for both drugs
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
Bile Acid Sequestrants : Colesevelam, Colestipol, Cholestyramine
MOA?
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
Bile Acid Sequestrants : Cholesterol reduction efficacy?
LDL : decr by 15-26%
TG : MAY INCR!! avoid in TG levels exceeding 300 mg/dL
A1C : Decr by 0.5%
BA sequestrants : AE’s ? (5)
Which forms are better tolerated?
DDI’s?
-impaired abs of?
-Reduced Bioavail of?
-Avoid DDI’s by??
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
BA sequestrants : CI? (2)
What are the pros?
bowel obstruction
Hx of hypertriglyceridemia-induced pancreatitis
It can lower A1c and its safe in pregnancy
Dosing for the following :
- Colesevelam (Welchol)
- Cholestyramine (questran)
- Colestipol (Colestid)
- 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)
- 8-16 grams po daily, divided into 2 doses
- 2-16 g po daily in 1-2 divided doses
Third Statin Benefit Group - Diabetes
- What are some ASCVD risk enhancers? (6)
- Lipid biomarkers?
- In select individuals if measured : Hs-CRP , LP(a), ApoB, ABI
- Kim, see chart for diabetes protocol !
- 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) - persistently elevated triglycerides (>175 mg/mL)
- > 2 mg/L,
LP(a) > 50 mg/dL
ApoB >= 130 mg/dL
ABI < 0.9 (bad)
New LDL-C Lowering Pharm Therapies : Inclisiran
MOA?
Small interfering RNA (siRNA) molecule that reduces the production of pcsk9 by inhibiting mRNA
Inclisiran :
Cholesterol reduction efficacy?
AE’s? (2)
Dose?
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
ACL (Adenosine triphos citrate lyase) inhibitors (Bempedoic Acid)
MOA?
Inhibs ACL which lowers LDL-C by inhibition of cholesterol synthesis upstream of HMG-CoA
ACL Inhibs (Bempedoic Acid)
1. Lowers LDL by how much in combo with statin?
2. In combo with Zetia AND statin?
AE’s ? (6)
- 17-18%
- 38%
URTI,
muscle spasms
hyperuricemia
back pain
abdominal pain/discomfort, elevated liver enzymes
ACL Inhibs : Dosing
- Bempedoic acid (Nexletol)
- Bempedoic acid/ezetimibe (Nexlizet)
- 180 mg po daily w/or without food
- 180 mg/10 mg po daily with or without food
HDL Targeter : Niacin
What is the MOA?
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
Niacin and how it affects the following :
TG, LDL-C, HDL-C
Major AE’s? (4)
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
AIM-HIGH Trial Niacin
Despite incr in HDL-C and favorable effects on lipid profile, what was not noted?
NO CV benefit seen!
Omega 3 Fatty Acids (DHA + EPA)
How does it effect the following? TG, TC, VLDL, HDL, LDL
TG : Decr 27-45%
TC : Decr 7-10%
VLDL : Decr 20-42%
HDL : Incr 8-14%
LDL : Incr is variable
Omega 3 Fatty Acids (DHA + EPA)
Major AE’s ? (5)
Dosing for Lovaza (Omega 3 acid ethyl esters) and Vascepa (Icosapent ethyl) ?
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
Fibrates : Gemfibrozil and Fenofibrate
MOA?
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
Fibrates : how does it affect the following
TG, HDL-C, LDL-C and TC ?
What are the ae’s ? (3) (GGM)
TG : Decr 20-25% (Good!)
HDL : Incr 10-15%
LDL and TC : Decr 20-50%
- GI upset
- May enhance formation of gallstones
- Myopathies (especially with gemfibrozil when used with statins - fenofibrate preferred w/statin use)
Gemfibrozil (LOPID) Dose?
Fenofibrate (Tricor) Dose?
what have clinical trials found?
- 600 mg BID 30 mins before breakfast and dinner
- depends on formulation
- They reduce coronary events as monotherapy but NOT when used in combo with statins
Familial Hypercholesterolemia : Management for
- HeFH ? (LDLC >190 mg/dL w/similar first degree relative)
- HoFH? (LDLC>400 mg/dL and 1 or both parents with Dx)
- high intens statins, PCSK9I, bempedoic acid
- Lipoprotein apheresis, evinacumab, lomitapide, evolocumab , statins reduce LDLc modestly even in those who are receptor negative
Evinacumab :
- MOA?
- LDLC, TC, ApoB, Non HDL, HDL?
- AE”s? (5)
- What has NOT been determined?
- hmAB binds and inhibs ANGPTL3. this is expressed in liver and involved in lipid metab by inhibiting LPL and EL.
- LDL decr by 49%, TC decr 48%, Apo B decr 37%, Non HDL Decr 52%, HDL Decr 30%
- Nasopharyngitis, rhinorrhea, influenza like illness, dizziness, nausea
- cardiovasc benefit
MTP Inhib (Lomitapide)
MOA?
LDLC, TC, ApoB, Non HDL?
Major ae’s?
what has not been determined?
- inhibs MTP, preventing assembly of apo B containing lipoproteins in enterocytes and hepatocytes (inhibits synthesis of chylomicrons and VLDL)
- LDL decr 40%, TC decr 30%, ApoB decr 39%, Non-HDL decr 40%
- Liver toxic. (incr ast/alt/alk phos/T bili); hepatic steatosis (BBW and REMS requirement)
-diarrhea, N/V/abd pain, vitamin deficiency - Cardiovasc benefit
Elderly Age > 75
- If already on statin what do u do?
- May be at higher risk for? SO do what?
- continue if tolerated
- Statin intolerance, initiate moderate intensity statin if necessary
Special Pop : Pregnant
- What’s safe?
- FDA removed CI for use of statins during pregnancy .
-Discuss some of the risk versus benefit situations (2)
- BA sequestrants
- Consider CONTINUING statin for those with clinical ASCVD , or HoFH
- COnsider HYDROPHILIC statin (Pravastatin) over lipophilic statin
PT’s with CKD not on Hemodialysis
- Have higher risk of ?
- Still benefit from ?
PT’s with CKD ON HEMODIALYSIS
- Benefit???
- ASCVD
- Statin use for primary prevention
- no signif benefit in vascular outcomes! Initiation is NOT recommended
Kim, See Chart for 4th statin benefit group
Primary prevention
