Lipid Meds

normal physiologic function of cholesterol

structural component of cells

precursor in hormone synthesis

used in bile acid production

HLD is an excess of _

cholesterol, cholesterol esters, TGs, phospholipids

3 main cholesterol types

HDL

LDL

TGs

LDL function

carries cholesterol to arteries

apoprotein found on HDL

ApoA and C

cholesterol pathway

food → intestines → chylomycrons → TG distribution to tissues → liver → bile acids

the ASCVD risk score is predicting _

10 year risk to FIRST event

what are the risk categories/cut offs for ASCVD

low: less than 3%

borderline: 3-5%

intermediate: 5-10%

high : 10%

LDL level to use the ASCVD risk score

70-189

general population lipid panel goals

Total < 200

HDL > 60

LDL < 100 or <70 if high risk

TG <150

previous ASCVD event lipid panel goals

total <200

HDL > 60

LDL <70 or <55 for very high risk

TG <150

age group for primary prevention

30-79

5 risk enhancers of dyslipidemia

FH of early onset ASCVD

South Asian/filipino ancestry

chronic inflammatory diseases

TGs persistently elevated

LDL persistently >160-189

non-HDL >190-219

age for early onset ASCVD

men: <55

women: <65

algorithm for adults with DM without ASCVD is broken down based on _

age

what to consider for age 20-39 with diabetes without ASCVD

diabetes specific risk enhancers?

30+: PREVENT score >3% / 30year >10

start _ for higher risk 20-39 yo’s with diabetes without ASCVD

moderate intesity statins

diabetes risk enhancers

long duration

albuminuria > 30

egfr <60

retinopathy

neuropathy

ankle-brachial index <0.9

criteria for defining very high risk

2 or more ASCVD events

1 event + 2+ high-risk conditions

start _ for very high risk adults

high intensity statinv

very high risk lipid goals (2+ ASCVD events)

50% reduction in LDL

LDL <55

non-HDL <85

high risk lipid goals (1 event + 2 high risk conditions)

50% reduction in LDL

LDL <70

non-HDL <85

dietary fat recommendation

total fat 25-35% of total calories

saturated fat 7% of calories

dietary cholesterol recommendation

<200 mg/day

dietary fiber recommendation

20-30 g/day

OTC therapy for non-pharma treatment

fiber

plant sterols

statins block the conversion of _

HMG-CoA to mevalonic acid

pleiotropic effects of statins

improved endothelial function

stabilize plaques

decrease oxidative stress

high intensity statins LDL lowering percentage

> 50%

moderate intensity statin LDL lowering %

30-49%

low intensity statin LDL reeduction %

<30%

which are the high intesntiy statins

atorvastin

rosuvastatin

which statins are hydophillic

rosuvastatin

pravastatin

statins with a short half life

lovastatin

simvastatin

fluvastatin

pravastatin

which statin causes most myopathy

simvastatin 80 mg

which statins DON’T need renal adjustment

atorvastatin

pravastatin

CYP3A4 statins

lovastatin

simvastatin

atorvastatin

statins have drug interactions with _

strong CYP3A4 INHIBITORS

drugs that interact with statins (besides CYP3A4 inhibitors)

warfarin

bile acid sequestrants

fibrates

niacin

anti-arrythmatics

colchicine

who is at increased risk of statins myopathy

age 65+

high dose statins

impaired renal function

strong CYP3A4 inhibitors

management of statin myopathy

lower the dose

switch statins

reduce frequency

discontinue

monitor CPK if rhabdo is a concern

monitor for myopathy in patients taking a statin and _

colchicine

simvastatin drug interactions that require limiting

verapamil/diltiazem

amioadrone

amlodipine

ranolazine

ticagrelor

ticagrelor simvastatin limit

40. mg simvastatin

verapamil/diltiazem simvastatin daily limit

10 mg

Amiodarone/amlodipine/ranolazine simvastatin dosing limit

20 mg

statins pregancy recommendation

if not at high risk, statins should be stopped 1-2 months before conception or as soon as becoming pregnant

AND discontinued while lactating

which pregnant patients can continue statins

those with familial hypercholerolemia

clinical ASCVD

high risk pregant patients statin choice

hydrophillic statins (pravastatin, rosuvastatin)

contraindications of statins

acute liver disease

pregnant/breast feeding

strong CYP3A4 inhibitors

4 adverse effects of statins

myopathy

arthralgias

rhabdo

hepatotoxicity

monitoring for statins

LFTs at baseline

lipid panel at baseline and 4-12 weeks after initiation/dose change → q3-12 months

ezetimibe drug class

cholesterol absorption inhibitors

ezetimibe MOA

inhibits NPC11 transporter in the small intestine → reduces dietary and biliary cholesterol absorption → lowers LCL

• up regulation of LDL receptors

initial non-statin drug

ezetimibe

indication of ezetimibe

initial non-statin therapy

people with statin intolerance

add on for those with FH

ezetimibe contraindications

active liver disease

pregnant/lactating

strong CYP3A4 inhibitors

adverse effects of ezetemibe

pain in extremeties

diarrhea

URIs

monitoring for ezetimibe therapy

lipid panel at baseline and 4-12 wks after → q3-12 mo

how does ezetimibe affect cholesterol delivery

decreases delivery to the liver while increasing clearance of cholesterol from the blood

list the PCSK9 inhibitors

inclisiran

alirocumab

evolocumab

PCSK9 normal function

promotes LDL-R degradation within the liver

_ are primary receptors to clear circulating LDL

LDL-R

inclisiran MOA

siRNA targets PCSK9 mRNA and reduces PCKS9 synthesis

what is noteable about inclisiran administation

needs to be done by a healthcare professional

which PCSK9 drugs are monoclonal antibodies

alirocumab

evolocumab

alirocumab/evolocumab MOA

PCSK9 monocolonal antibodies inhibit the binding of PCSK9 to the LDL-R

PCSK9 inhibitors 3. indications

1. add on to statin

2. high risk patients intolerant to statins

3. patients with FH on max tolerated statin + ezetimibe

administation of PCSK9 monoclonal antibodies

patient can self-admin at home

contraindications of PCSK9 inhibitors

hypersensitivity

AEs of PCSK9 inhibitors

injection site reactions

nasopharyngitis/URIs

UTIs

evolocumab specific AE

back pain

alirocumab specific AE

LFTs

inclisiran specific AEs

arthralgia

bronchitis

PCSK9 inhibitors monitoring

lipid panel at baseline and 4-12 wks after initiation/change → q3-12 months

caveat of prescribing PCSK9 inhibitors

can be costly and require prior authorization

MOA of bile acid sequestrants

binds bile acids in intestines → forms complex → secreted in stool

increased conversion of liver cholesterol into bile acids to reduce intra-liver cholesterol

upregulation of LDL-R as a compensatory measure to the low liver cholesterol

3 bile acid sequestrant drugs

colesevelam

cholestyramine

colestipol

indications for bile acid sequestrants

ALTERNATIVE in patients who are ezetimibe intolderant with TG <300

contraindications of bile acid sequestrants

bowel obstruction

complete biliary obstruction

HTG induced pancreatitis

elevated TGs >500

colestipol contraindications

complete biliary obstruction

bowel obstruction

colesevelam CIs

bowel obstruction

bile acid sequestrants bind _ (as an adverse effect)

other negatively charged drugs

AEs of bile acid sequestrants

constipation/ GI upset

tooth discoloration

hyperchloremic acidosis

increase TGs

cholestyramine specific AE

tooth discoloration and enamel decay

monitoring for bile acid sequestrant

lipid panel at baseline, then 4-12 weeks, then q3-12 months

• TG if concerned for HTG

timing of administering bile acid sequestrants

1 hour before / 4-6 hrs after other oral meds

bile acid sequestrant pregnancy category

safe in pregnancy

bile acid sequestrant drug intrxns

OCPs

warfarin

digoxin

fat-soluble vitamins

which bile acid sequestrant has shown CV benefit

cholestyramine

bempedoic acid drug class

adenosine triphosphate citrate lyase inhibitor (ACL-i)

ACL-i drug

bempedoic acid

bempedoic acid MOA

inhibits ACL → decreases liver cholesterol synthesis → up regulates LDL-r → decreases serum LDL

Prodrug activated by very long-chain acyl-CoA
synthetase, found primarily in the liver

bempedoic acid

indication of bempedoic acid

adults with clinical ASCVD or FH as ADJUNCT to max statin or alternative agent in patients intolerant of other lipid-lowering agents

bempedoic acid has _ benefits

cardiovascular

bempedoic acid is available as a combo product with _

ezetimibe

avoid _ in combo with bempedoic acid

simvastatin >20mg

pravastatin >40 mg

only newer oral non-statin with CV benefit

bempedoic acid

bempedoic acid contraindications

none