cholesterol and statins

includes part 1 and 2

most significant consequences of dyslipidemia

premature coronary atherosclerosis

manifestations of ischemic heart disease

*risk is directly related to degree of LDL and TC elevation

the term “lipids” includes:

cholesterol

triglycerides

phospholipids

TC optimal level

<200 mg/dL

TC high level

>/= 240 mg/dL

TG optimal level

<150 mg/dL

TG high level

200-499 mg/dL

TG very high level

>500 mg/dL

LDL optimal level

<100 mg/dL

LDL high level

160-189 mg/dL

LDL borderline high level

130-159 mg/dL

LDL very high level

>/= 190 mg/dL

HDL optimal level males

>40 mg/dL

HDL optimal level females

>50 mg/dL

apolipoproteins

required for assembly/secretion of lipoproteins

embedded on the surface of each lipoprotein

cofactors for certain enzyme activation

ligands for binding receptors on cells

chylomicrons purpose

deliver TGs

increased intracellular cholesterol leads to _____ synthesis of LDL receptors

decreased

dyslipidemia definition

one or more of the following:

elevated TC

elevated LDLs

elevated TG

low HDLs

LDLs >250 can lead to:

corneal arcus of the eye

xanthomas

TGs >1000 can lead to:

pancreatitis

tuberoeruptive xanthomas

statins are also known as:

HMG-CoA reductase inhibitors

low intensity statins list

simvastatin 10

pravastatin 10-20

lovastatin 20

fluvastatin 20-40

*reduces LDL-C by <30%

moderate intensity statins list

atorvastatin 10-20

rosuvastatin 5-10

simvastatin 20-40

pravastatin 40-80

lovastatin 40-80

fluvastatin XL 80

fluvastatin 40 BID

pitavistatin 1-4

*reduces LDL-C by 30-49%

high intensity statins list

atorvastatin 40-80

rosuvastatin 20-40

*reduces LDL-C by >50%

statins MOA

inhibits convertsion of HMG CO-A to L-mevalonic acid and subsequently cholesterol

lowers LDLs and TGs

raises HDL

statins that work with 3A4 list

lovastatin

simvastatin

atorvastatin

lipophilic statins list

lovastatin

simvastatin

fluvastatin

atorvastatin

pitavistatin

non-lipophilic statins list

pravastatin

rosuvastatin

statins that work with 2C9 list

fluvastatin

rosuvastatin (also 2C19)

statin that works with UTG1A3/2B7

pitavistatin

statin that does not work with an isoenzyme

pravastatin

statins with active metabolites

lovastatin

simvastatin

atorvastatin

rosuvastatin

ADRs of statins

statin-associated muscle symptoms (SAMS): myalgias, rare myopathy and rhabdo

diabetes

liver toxicity

memory/cognition decline in rare cases

statins monitoring

baseline tests: lipid panel, renal function, CK, LFTs

repeat fasting lipids 4-12 weeks after initial statin therapy, then q3-12 months

statin safety

no new pts on simvastatin 80

pts already on it may stay on it if they have been on it for >1 year w/o ADRs

contraindicated with:

• azole antifungals

• macrolides (except azithromycin)

• protease inhibitors

• nefazadone

• cyclosporine

• danazol

• gemfibrozil

do not exceed 10mg of simvastatin if you take:

verapamil

diltiazem

do not exceed 20mg of simvastatin if you take:

amiodarone

amlodipine

ranolazine

primary prevention for LDL >/= 190

high intensity statin

if LDL remains >/= 100 → zetia

if LDL remains >/= 100 with the zetia and statin → PCSK9 inhibitor

primary prevention for adults with LDL <190 and diabetes

moderate intensity statin

• if adult is high risk (10-yr risk score >/= 7.5%) → high intensity statin

moderate or high intensity determined based on 10yr ASCVD score

primary prevention for adults 40-75 years old without diabetes and LDL <190

use ASCVD score

• <5% = low risk (lifestyle modficiation)

• 5-7.5% = borderline risk (moderate statin possible if risk enhancers present)

• 7.5-20% = intermediate risk (moderate statin)

• >20% = high risk (high intensity statin)

diabetes-specific risk enhancers independent of other risk factors in DM for a cardiovascular event

long duration of having the diseasealbuminuria

eGFR <60

retinopathy

neuropathy

ankle brachial index < 0.9

CAC (coronary artery calcium) score

score that shows the buildup of calcium to predict levels of atherosclerosis

lower CAC = lower risk

CAC score can be considered a risk enhancer

absorption inhibitor

zetia 10mg qd

MOA: blocks cholesterol absorption across intestines, upregulates LDL receptors

ADRs: well-tolerated

caution with: liver disease

place in therapy: in combination with other pharmacotherapy, is usually the second add behind a statin

PCSK-9 characteristics

created + released from the liver

breaks down LDL receptors to be recycled

PCSK-9 inhibitors

prevents the breakdown of LDL receptors, decreasing the overall blood concentrations of LDL

includes: praluent, repatha

praluent/alirocmab

PCSK-9 inhibitor

dosing: 75mg q 2 weeks, can be increased to 150mg q 2 weeks

used as an adjunct to max tolerated statin and zetia to reduce risk fo ASCVD events

repatha/evolocumab

PCSK-9 inhibitor

dose: 140mg q 2 weeks or 420mg q month

similar indications to praluent

bempedoic acid/nexletol

MOA: inhibits ATP citrase lyase, upstream from HMG-CoA reductase

reduces LDL by 20-25%

ADRs: gout, hyperuricemia

no contraindications

used in combination with other pharmacotherapy

dose 180mg qd

inclisiran/leqvio

MOA: siRNA that prevents formation of PCSK-9

LDL reductio of ~50%

ADRs: injection site rxns, antibody development, arthralgia

no contraindications

used in combination with other pharmacotherapy

dose 284mg q6 months

bile acid sequestrants

includes: cholestyramine, colestipol, colesevelam

MOA: binds bile acids in intestinal human, depleting the hepatic pool of cholesterol to increase LDL receptors and cholesterol synthesis

ADRs: GI

can decrease bioavailability of acidic rugs

used in combination with other pharmacotherapy

pharm therapy approved for TG levels >/= ____ mg/dL

500

fibric acid derivatives

includes: fenofibrate, gemfibrozil

MOA: unsure, increases VLDL clearance and decreases its synthesis

causes slight increase in HDLs, whcihc can cause a reciprocal rise in LDLs

~40-50% lowering in TGs

ADRs: GI, myopathy

caution with: renal insufficiency, gallbladder disease, liver/renal dysfunction

used for hypertriglyceridemia

which fibric acid derivative can NOT be used with a statin?

gemfibrozil

which fibric acid derivative can be used with a statin?

fenofibrate

concentrated fish oils (EPA/DHA)

includes: lovaza, vascepa, epanova

MOA unclear: may reduce TG synthesis like fibrates

ADRs: GI, fishy taste, platelet aggregation effects

caution with: renal, liver, gallbladder disease

used for hypertriglyceridemia

nicotinic acid/niacin

MOA: reduces hepatic synthesis of VLDL and therefore LDL

all trials show no CV benefit whatsoever

ADRs: flushing, GI, hepatotoxicity

caution with: uncontrolled diabetes, gout, contraindicated in active liver disease

used in mixed dyslipidemia, hypertriglyceridemia

meds used for genetic cholesterol abnormalities (HoFH)

mipomersen and lomitapide

agents that do NOT have clinical trial evidence for reduction in CV events

niacin

inclisiran

mipomersen

lomitapide

agents that do have clinical trial evidence for reduction in CV events

ezetimibe

bile acid sequesterants

fibrates

omega-3 fatty acids

PCSK-9 inhibitors

bempedoic acid