Dyslipidemia Managment Flashcards
difference between cholesterol and triglycerides
role of lipoproteins
Cholesterol
- used for cell membrane flexibility
- vitamin D synthesis
- sex hormone production
- use in bile acid
Triglycerides
- used as energy!
- directly transported to the muscles
- stored in adipose tissue later for energy
these cant circulate in the body alone– need to be packaged in lipoproteins to travel
different lipoproteins contain differnt amounts of triglyceride and cholesterol
chylomicron: majority TG (80-95%)
VLDL: 55-80% TG
LDL: 60-70% cholesterol
HDL: low amounts of both cholesterol and TG
apolipoprotein (non-HDL) are the lipid delivery pathway made from the liver or metablism
Apo-a-1 protiens: (HDl) are part of reverse lipid trasnport from cells back to the TG or cholesterol form
- reverse cholesterol transport back to liver
- reverse cholesterol to exchange with the others (LDL, VLDL, etc.)
formation of LDL (smaller particles) from VLDL and chylomicrons —> release TG (as fatty acids) as they change into LDL
LDL taken up by liver or peripheral cells (turning into an atherosclerotic palque!!!)
what constitutes atherosclerotic cadriovascular disease (ASCVD)
how do VLDL, LDL and chylomicrons play a role
cholesterol causing ischemia!!
- MI
- TIA/Stroke
- stable or unstable angina
- cornary/arterial revascularization
- PAD
things due to atherosclerotic origin a clot issue
LDL – increased LDL = increased cholesterol = atherosclerosis
VLDL – increased VLDL = increased TG = atherosclerosis (because its on itsway to become a LDL)
Chylomicrons – increased chylomicrons = incread TG = acute pancreatitis (want TG < 500)
non-pharm recommendations too…
- lower LDL
- lower TG
- raise HDl
- reduce ASCVD risk
lower LDL
- increase fiber
- phytosterol supplementation
increase HDL
- increase exercise
- stop smoking
Raise HDL
- loose weight
- increase exercise
- stop drinking alcohol
- reduce sugar and carb intake
Lower ASCVD
- avoid trans fats
- increse veggies and fruit
- reduce intake of cholesterol and sodium foods
- get exercise
- stoke smoking
Statins
- MOA
- when are they used
- what groups of people benefit from statin use
Statins- focus on lowering LDL levels by 18-55%
MOA
- specifically: works to decrease the amount of cholesterol being produced within the liver –> therefore forcing the liver to increase the amount of receptors it has on its surface to attract more out of the serum!
- act by blocking HMG-CoA reductase to stop the prodcution of cholesterol in the liver
Purpose
- to lower the ASCVD risk for individuals – #1 treatment choice
- they lower LDL, non-HDL lipoproteins & TG
- additionally –> can stabilize a pre-formed atherosclerotic plaque, and decrease inflammation
- inhibits platlet aggregation & thrombin generation
- depending on risk factors – used as moderate or high dose therapy
- atorvostain and rousuvastain= can be high dose treatment
Populations who benefit
- secondary prevention: for those who have HAD an ASCVD event ( MI,stroke,PAD or revascualrization) –> give high intensity statin
- primary prevention:for those…
- 1. who have severe hypercholesteremia ( LDL > 190)
- 2. who have DM (age 40-75) & LDL > 70
- 3. who have ASCVD risk score > 7.5% & LDL > 70 (age 40-75)
how to differentiate between high risk and very high risk ASCVD in secondary prevention
treatment pathways for each
considered to be VERY high risk ASCVD if…
1. history of 2 major ASCVD events (MI/stroke,etc.)
OR
2. 1 major ASCVD event + 2 high-risk conditions (older lage, DM, HTN, CKD, smoker)
(*if not of the above, but still had ASCVD at any point – they’re just “high risk secondary prevention”)
Treatment
VERY high risk ASCVD
- initiate high intensitity statin
- if LDL still > 70 = add ezetimibe
- if STILL LDL > 70 = add PSK-9 inhibitor
High Risk ASCVD
- initiate high intensitiy statin
- if LDL still > 70 = add ezetimbie
remeber thresholds are not goal thearpies – just when to consider stepping up treatment
the only goal is the % reduction in LDL by statins
treatment decisions for severe hypercholesteremia (LDL > 190) in primary prevention
what type of PCSK9 for heterzygote or homozygote FH?
PRIMARY PREVENTION: pt. has LDL > 190
1. start them immediately on a high intensity statin treatment (no need for the ASCVD risk score tool here)
if the LDL is > 100 still….
2. add ezetimibe
if the LDL is STILL > 100….
- add PCSK9inhibitor or
- bempedoic acid or
- bile aceid seqestrant
pts. with this high of LDL may have familial hypercholesterolemia….
heterozygote: do statin + (alirocumab or bempedoic acid)
homozygote: statin + evolucumab
in severe primary hypercholesteremia, what non-statin meds can we use?
how do they work? MOA
PCSK9 inhibitors (alirocumab = hetero) or Evolocumba = for heterzygote or homozygote pts. age 10+
Ezetimibe (off-label use): in homozygotes age 10+
Bile acide sequesterants: in heterozygotes ages 10-17
treatment decisions for those
primary prevention
ages 40-75
DM
- start mod. intensty statin
- can calcuate ascvd score, if its >20% or they have lots of risk factors = start a high intensitiy one
after starting hig-intensity – still not redcued LDL by 50%? add ezetimibe
treatment decisions for
primary prevention
LDL > 70
age 40-75
no DM
if ascvd < 5% = lifestyle changes
if ascvd 5-7.4% + risk factors = mod. statin
if ascvd 7.5-19.9% + risk factors = mod statin
ascvd 20% = high intensity
risk factors include
- CKD
- metabolic syndrome
- south asian
- inflammatory disease
- preeclampsia
primary prevention
pt. 40-75
LDL > 70
no DM
but the risk factors are mehhh
and then ascvd risk score is intermediate
what do you do
look at cornary artery calcium score
for those in boardeline or intermediate risk ASCVD groups
CAC = 0 reassecc score in 5-10 years
CAC = 1-99 favors use of statin
CAC = > 100 or 75% occulsion initiate statin
how do you monitor lipids
when do you recheck
recheck lipid panel after 4-12 weeks of initiating or adusting meds
if the goal % drop is achieved — > continue and reassess in 3-12 months
if the goal % drop is not –> assess other causes, reinforced med adhearace and repeat 4-12 weeks
still no? inc. statin or add meds
Statins
drug names
who is metabolized at CYP3a4
how does tirating the statin dose up help?
Atrovastatin & rousuvistatin = can be used at high does
- avoid use of simvistatin and lovastatin – too many interactions
who is metabolized at 3A4? so careful with cyp3a4 inhibitors!! (azoles)
- lovastatin
- simvistatin
- atrovastatin
avoid statin use with gemfibrozil
dont drink more thant 1 quart of grapefruit juice a day
how dose doubling the dose work?
- will only increase the amount of LDL lowering by 6%
special populations and statin use
asians should avoid what? use what dose of other?
japanese should do what
pregnant
children
Asian
- avoid simvastatin!!
- use rousuvastatin starting low dose 5mg
Japanese
- may require lower doses of statins
- rousuv., pravas & pita
pregnant
- usually stop
- but high risk pt. assess risks
children
- rousuvistatin: can be used at age 8 (7 if FC)
- prava and pita: 8 years
- lova, simva & ator: 10 years
Statin adverse effects
3 big ones
who is at risk for these
what is statin intolerance?
- SAMS- statin assocaited muscle symptoms
- myalgias, myopathy, rhabdomyolysis - increased liver enzymes
- transient – monitor baseline prior to initial dose - new DM
- increased risk with increased dose
who is at risk for these?
- those with co-morbid (liver and kidney issues)
- previous muscle or statin issues
- unexaplined ALT elevation
- drug-interactions
- older thant 75
- asians
- the dose of the stain plays a big role here
have a side effect? retry it and see
Statin Intolerance
- people who tried statins a minimum of at least 2 different kinds, with one at their lowest dose and still couldnt handle it
find the max they can tolerate and maybe leave there (or add non statin)
what is monitored during statin treatment
- if they present with muscle symptoms = check creatine
- if they have signs of hepatotoxicity = check liver enzymes and bilirubuin/alk. phosphate
no routine measurement of these is necessary
what is bempedoic acid
- when is it used
- moa
- councel pts. with what
- avoid with what
Bempedoic acid
- an ACL inhibitor: upregualtes the LDL receptors on the liver to decrease LDL in the serum (reduces cholesterol in the liver further up the stream than the statins (at hmg-coa) do
- could have less effects on muscles because they dont have the receptor it works at – where statins act at a receptor the muscles have too (leading to side effects)
used in addition to statin treatment for those with HeFH or established ASCVD needing more
avoid with
- simvastatin
- pravastatin
councelling..
- tendon rupture
- gout!!!: can worse it because impacts uric acid
Ezetimibe
- moa
- when is it used
- adverse reaction
used as add-on therapy with a statin to increase lowering of LDL if they are not at the threshold, this is better than just increasing teh dose of the statin!
MOA
- inhibit absorbtion of cholesterol in the INTESTINES at the brush boarder –> decrease cholesterol into th eliver –> increased receptors on the liver for LDL –> takes more out of the serum
- could be used monotherapy if statin intolerant
Adverse events
- arthraligas, liver enzymes (but is is the statin?)
- GI upset
- no need for renal or hepatic adjustments
PCSK9 inhibitors
- when are they used
- MOA
Specifics of inclisiran
work for those with secondary VERY high risk ASCVD with LDL still > 70 & work for familial HC heter and homozygotes
these are monoclonal antibodies –> block the chaperone protein (PCSK9) from breaking down the LDL receptors on the liver – thus more receptors means more uptake of LDL into the liver & lower LDL in the serum!
alirocumab = good for high risk ascvd pts. & heterzygote HC
Evolocumab = good for High risk ASCVD & hetero or homozygotes HC
Inclisiran
- a siRNA med injection Q6months
- used for heterozygotes HC who need additional LDL lowering
Bile Acid sequesterants
MOA
when to use
names
side effects
contraindications
add-on treatment for those with high LDL & cant use statins or for familial heterzygotes in ages 10-17
MOA
- increases bile acid secretion –> increases conversion of cholesterol into bile acie –> increases liver uptake of the cholesterol
names
- colesevelam
- colestipol
- cholestyramine
side effects
- GI related (not systemtically absored– work only in GI)
- take with meals! mix with liquid
contraindications
- history of bowel obstruction
- TG > 300
monitor
- TG, LDL & ADRs
- many D-D interactions!! not used….
what are the two goals to treating high triglycerides
- reduce ASCVD risk by lowering atherogenic particles (those with LDL, VLDL, etc.) — we want to use these meds in addition to statins to lower LDL levels
icosapent ethyl > fibrates > omega 3 FA > niacin
Reduce the risk of pancreatitis (occuring with TG > 500)
any drug (but niacin) will do this
secondary causes of dyslipidemia
diet related (too much fat and carbs)
poor exercise & overweight
alcohol
drugs (steroids, dieurietics, amioderone,oral estrogen)
pregnancy
uncontrolled DM is most common
obesity
hypertriglcerides
what is fasting triglyceridemia?
- define as….
- treatment groups
fasting hypertriglycerides = persistent fasting TG after…
1. FTG > 150 after 4-12 weeks of interventions (lifestyle)
2. stable dose of an already maxed statin
3. ruled out secondary causes of High TG
manage the TG levels in….
1. ASCVD (those who have had) pts. with TG 150-499
2. DM, age 40+ with TG 150-499
3. no DM, age 40+ with TG 150-499
4. age 20+ with TG > 500
first: must rule OUT a secondary cause of high TG & have optimized treatment via lifestyle and diet first
lifestyle modifications to make to attempt to lower TG before starting additional pharm treatments
- if TG 150-499
- if TG 500-999
- if TG > 1000
if TG 150-499
- total fat : 30-35%
- added sugar < 6%
- restricit alcohol
- lose 5-10% of body weight (for all groups)
if TG 500-999
- total fat : 20-25%
- < 5% sugar
- NO alcohol
If TG 1000+
- 10-15% total fat
- no sugar
- no alcohol
TG management for…
ASCVD pts. with TG 150-499
- rule out 2ndary cuases and fix diet and lifestyle
- glycemic control
- use statin (high-intensity) and adhearance
THEN…
- if LDL >100 —> use non-statin LDL therapy lowering (ezitamibe??)
- if LDL 70-99 —> LDL or TG lowering non-statin thearpy
- if LDLD < 70 —> use icosapent ethyl
icosapent ethyl = omegat-3-fatty acid Rx. (?)
TG management for…
DM, age 40+ & TG 150-499
- r/o 2ndary causes
- optimize glycemic control!!!
- high-intensity statin (add on ezetamibe if ascvd >20%)
- if NO additional ascvd risk factors —> intensify the statin
- if 1+ ASCVD risk factor (and older than 50) –> add icosapent ethyl
TG management for…
age 20+, No DM ,TG 150-499
- r/o 2ndary causes
- max. lifetstyle and diet
- calcualte the ASCVD score & risk factors….
- if low risk < 5% = continue lifestyle modifications
- if intermediate 5-19.9% = discussion– consider statin
- if high risk - 20% = initiate statin
TG management for…
20+, with TG >500
- r/o 2ndary causes & max. lifestyle changes
- optimize glycemic control (in DM pts.)
- if TG 500-999 = calculate ASCVD score….
1. ASCVD > 5%, they have DM, or an ASCVD event = initiate or up the statin
2. ASCVD < 5%, they dont have DM or an ASCVD event = consider using fenofibrate or O3FA which will direclty target the TG alone (since there is minimal or no ASCVD risk– dont neeeed a statin here)
if TG > 1000 (obv. if the ASCVD risk is high use a statin here)
- but in the absence of the need for a statin (DM, high LDL, ASCVD) you can initiate ONLY fenofibrate or O3FA
Omega-3 Fatty Acids
- MOA
- uses
- Side Effects
- recommendations
MOA
used to lower TG (for TG > 500)
- lower VLDL and TG synthesis in the liver
- inhibit acetyle coA
names (containing EPA & DHA)
- icosapent ethyl
- O3FA carboxylic acid
- OSFA fatty acid ethyl
Side Effects
- GI upset
- increased LDL
- arthraligas
- bleeding
- increased risk of Afib/Aflutter
Recommendations
- take with food
- no renal or hepatic adjustments needed
fish oil OTC is NOT O3FA!!!!!
Fenofibrate
- MOA
- uses
- names
- Side Effects
- Drug interactions (two big ones)
MOA
- decrease apoCIII –> increases the metabolism of VLDL particles (which contain lots of TG)
- also reduce serum uric acid levels —increase the excretion of uric acid
Names
- gemfibrozil
- fenofibric acids
- fenofibrates
Uses
- for TG lowering abilities in those with TG > 500, (TG > 1000 and risk of panceratits) but statin use is maxed, or no risk of ASCVD is found)
Side Effects
- GI intolerance
- increase risk of gallstones
- transient LFT increase
- myopathy/myositis
- contraindicated: in severe CKD (eGFR < 30), gallbladder disease & liver disease
Drug INteractions
- CANNOT BE USED WITH STATINS!!!
- WARFARIN!!!!! it will enhace warfarins anticoagulation effect
Nicotinic Acids
- MOA
- used (rarely)
- side effects
- monitoring
MOA
- lower TG, LDL, TC, etc.
- increases HDL
- complicated: reduces rate of VLDL and LDL synthesis via blokcing production of FFA from adipose tissue
- downside: first past effect of liver significantly impacts these
Side Effects
- HEPATOTOXIC cannot use
- flushing
- skin issues
- glucose issues
it doesnt help with reducing CVD risk –> so we dont use it
Monitor
- LFTs
- lipids
- gluocse & uric acid for some pts.
