HLD therapeutics

Hyperlipidemia increases the risk of

CHD, stroke

CHD accounts for

1/7 deaths

how many americans on meds for hyperlipidemia?

more than half

how often to check cholesterol?

every 4-6y

atherogenesis steps

- Injury
- Inflam
- Fibrous Cap
- MPs cause rupture
- HA, stroke

in atherosclerosis ______________ build up under foam cells

lipids and plaque

atherosclerosis causes angina and SoB because

poor oxygenation

what does ASCVD risk calculator find?

10-year risk for 40-75 yo

which racial group highest risk for ASCVD?

African american

what are the greatest RFs for ASCVD?

smoking, high BP, diabetes

anything above ___________ cholesterol is dangerous

>130

must space fasting lipid panels by how long?

4-6wk

TG effect on CVD

- TG little effect on CVD
- mostly affect pancreas

Friedewald Formula

LDL = TC - HDL - (TG/5)

Clinical Presentation of HLD

- asymp
- metabolic syndrome
- symptoms of none to death
- signs of ab pain, pancreatitis, periph neuro, angina
- Labs

metabolic syndrome

- 3/5 of:
- HTN, insulin resist, ab obesity, prothromotic, atherogenic dyslipidemia

labs for HLD

- C-reactive protein
- lipid panel

Primary Hyperlipidemia

- genetics
- HoFH or HeFHyperchol

secondary hyperlipidemia

- diet
- drugs
- disease
- disorder
- most are a mixture

drug causes of hyperlipid

- steroids
- antipsychotics
- b blocker
- cyclosporin
- (weight gain)

nondrug causes of hyperlipid

- diabetes
- HIV
- anorexia
- preg
- malabs

the cornerstone of HLD therapy

dietary modification

HLD diet

- low trans fat
- high healthy fat
- fruit veg
- whole grain
- fish

other HLD lifestyle mods

- physical activity
- weight loss
- smoking cessation

goals of dyslipidemia treatment

- Correct lab abnorm
- Dec long term CV risk (prim and sec, and prevent prog)
- Prevent pancreatitis, HyperTG

primary prevention

treatment before ASCVD event

secondary prevention

treatment after ASCVD event

HMGCRs derive from

fungi

which statin from penicillium

mevastatin

which statin from aspergillus

lovastatin

red yeast rice

- low lovastatin
- little effect

what part of statins causes myalgias

Mevalonic acid

statin MoA

- inhib HMGCR
- inc LDL-r
- inc LDL removal

statins effects

- dec LDL
- dec TG
- inc HDL

pleiotropic effect is found in

- statins
- dec inflam and stabilize plaques
- dec risk CVD

statins CI

- liver disease
- preg X
- nursing

statins therapeutic uses

- dec risk
- nonfatal MI
- revasc
- stroke
- CVD mortality

statins indication

- HeFH HoFHyperchol
- prim and sec ASCVD

update on statins and preg

- CI nursing
- limit in preg
- ok for HoFH, estab ASCVD, high risk
- risk/benefit analysis

% pts intolerant statins

10%

statin AEs

- 25% myopathy
- rhabdo
- high LFT
- cog effects
- inc blood sugar and HbA1C

N of 1 statin study

% myalgias in placebo and statin are the same

RFs for statin AE

- mult comorb
- statin intol
- DDI
- >75y

why is age a statin AE RF

dec CL leads to inc AUC

Managing Statin Intolerance

- Dec and Rechallenge
- Rotate Statins
- Minimal Dose
- longer interval and long acting agents
- Lipophilic versus hydrophilic

dechallenge and rechallenge

stopping statin after AE and restarting on same dose or start on new drug low dose

which statin take with evening meal?

lovastatin

which statin take at bedtime?

- fluvastatin IR
- simvastatin

monitoring in statin therapy

- baseline LFT and FLP
- LFT initially q4-12wk
- LFT q3-12mo

statin 3A4 interactions

Atorvastatin
Lovastatin
Simvastatin

statin 2C9 interactions

Fluvastatin
Pitavastatin
Rosuvastatin

statin 2C19 interactions

Rosuvastatin

statin no CYP interactions

Pravastatin

high intensity statins

Atorvastatin 40-80
Rosuvastatin 20-40

statin therapeutic uses

Prim and sec ASCVD event

Jupiter trial

Rosuvastatin for prim (5-point MACE)

WOSCOPS trial

Pravastatin for prim

SPARCL trial

Atorvastatin for sec stroke

statin benefit groups

- clinical ASCVD
- LDL >190
- 40-75y w diabetes LDL 70-189
- 40-75y risk >7.5% LDL 70-189

sec >75 statin

mod intensity

sec <75 statin

high intensity

prim >190 LDL statin

high intensity

diabetes and risk >7.5% and LDL 70-189 and 40-75y statin

high intensity

diabetes and risk <7.5% and LDL 70-189 and 40-75y statin

mod intensity

prim prevent and >7.5% risk and 40-75y statin

mod or high intensity

LDL goal <70 for

- prev ASCVD event
- or familial hyperchol FH

LDL goal <100 for

- diabetes
- or ASCVD RFs

LDL goal <130 for

everyone else

ezetimibe MoA

- Blocks sterol transporter
- sm int brush border
- block abs

ezetimibe effects

- dec LDL
- dec TG
- inc HDL
- minimal

ezetimibe DDI

- space 2hr BABR
- inc cyclosporine

ezetimibe AE

- few
- combo best tolerated is statin

ezetimibe monitoring

LFT

Ezetimibe indications

- HoFH
- Homo sitosterol
- Prim hyperlipid
- Sec ACS

IMPROVE-IT trial

- ezetimibe and simvastatin
- dec CV event in pts at LDL goal
- combo > mono
- but other trials show no benefit

BABR mechanism

Bind BA in int and exc feces

BABR effects

- dec LDL
- inc HDL
- slight inc TG

BABR AE

constipation, bloating, flatulence

BABR DDI

dec abs fat solub vitamin

which drug is 1st line in preg

BABR

when to take meds w BABR

1h before or 4h after BABR

do not start BABR if

- TG >300
- pancreatitis bcs inc TG

discontinue BABR if

TG >400

BABR powder

- not as well tolerated
- use if can't swallow pills

BABR drugs

- Cholestyramine powder
- Colestipol powder
- Colesevelam tab

BABR off label

- for SEs
- diarrhea
- diabetes

PCSK9i MoA

- mAb
- inhib destruction LDL-r
- inc LDL

PCSK9i effects

- 60% dec LDL
- dec TG

PCSK9i trial

slight dec CV death after ACS (sec)

PCSK9i AE

- nasopharyngitis
- allergic rxn
- injection rxn
- some liver

PCSK9i indication

- HoFM mono
- Prim hyperlipid
- Sec Prevent CV event w estab CVD

PCSK9i drugs

- Alirocumab (Praluent)
- Evolocumab (Repatha)

which is the only drug for 1st line HoFH?

PCSK9i

which product is available SC monthly?

Evolocumab (Repatha) PUSHTRONEX

downside of PCSK9i

expensive

Inclisiran MoA

- small interfering RNA (siRNA)
- dec prod PCSK9 by inhib mRNA

which drug is billed through medical insurance?

- Inclisiran
- SC in office
- good for adherence

Inclisiran effect

dec LDL 50% combo high intensity statin

Inclisiran indications

adj in HeFH or ASCVD

ORION-4 trial

- Inclisiran
- effect on ASCVD