Cardio Exam 2- Madras

When do you do a lipid panel

Fasting

Low-density lipoprotein (LDL)

• major atherogenic lipoprotein (carries 60-70% of blood CHO)

• main target for lipid-lowering medications

high-density lipoprotein (HDL)

• happy cholesterol

• anti-atherogenic effect

Causes of reduced HDL

smoking, obesity, sedentary lifestyle, beta-blockers

causes of increased HDL

smoking cessation, moderate alcohol ingestion, physical exercise, weight loss, oral contraceptives, phenytoin

Apolipoproteins

• structure to lipoprotein

• receptor binding

• activate enzyme system

chylomicrons made of

triglycerides

Resulting Medical Conditions

MI, angina, arrhythmias, stroke, peripheral arterial disease, abdominal aortic aneurysm, sudden death

High TG puts you at risk for

pancreatitis

what causes hypercholesterolemia

thiazides, cyclosporine, glucocorticoids, protease inhibitors, isotretinoin, beta-blockers, progestins, mirtazapine, sirolimus

Non-pharm

diet, regular exercise, decrease body weight (10% body weight), stay away from saturated fats, smoking cessation, lower BP

Plant Sterols/Stanols

• Benecol and Take Charge

• lower LDL

• GI side effects

Bile Acid Sequestrants Ex

Colestipol, cholestyramine, colesevelam

Main effects of bile acid sequestrants

bind bile acids, send signal to liver (need more), drop liver supply of cholesterol = lower LDL BUT they can raise TG (bad)

Colesevelam different indication

help with glycemic control in type 2 DM; contraindicated in bowel obstruction and TG >500

Colestipol dose

start 5gm QD or BID or 2gm QD or BID

max 30gm/day granules or 16gm/day tablet

cholestyramine dose

take with meals

start 4gm QD or BID

max 24gm/day

colesevelam

take with meals

3.75gm/day in 1-2 divided doses

colestipol and colesevelam granules for oral suspension counseling point

do NOT take in dry form

cholestyramine suspension counseling point

do NOT sip or keep in mouth for long time —> may cause tooth discoloration and enamel decay

bile acid sequetrants interactions

• take 1-4 hours before or 4-6 hours after bile acid sequestrant

• colesevelam: decrease binding affinity for other drugs

when to take IR lovastatin

evening meal

when to take ER lovastatin

take in evening at bedtime

max effect seen in statins

in about 6 weeks

stations MOA

inhibit HMG CoA reductase —> increase synthesis of cell surface LDL receptor —> increase LDL blood clearance

what are the two high intensity statins

atorvastatin and rosuvastatin

when to take simvastatin

in the evening

Rosuvastatin is preferred in which patients

asian

statins can cause

• myopathy or increased muscle injury at 80mg

• 80mg should only be used in pts who have been taking this dose ≥12months with no muscle toxicity

which statin needs adj in renal impairment

lovastatin, pravastatin, simvastatin, rosuvastatin (40mg), pitavastatin (not indicated to reduce CV morbidity & mortality)

rosuvastatin indication

primary prevention of CVD

secondary prevention

already had a CV event

Statin Adverse effects

• increase HBA1c and fasting glucose levels reported with statin

• ADA Guidelines: may elevated type 2 DM risk if at elevated risk of developing type 2 DM —> monitor glucose status regularly and DM prevention reinforced —> not recommended statins be D/C

What test(s) do you do before initiating statin and as clinically indicated thereafter

• ALT, AST (liver enzyme tests), total bilirubin, and alkaline phosphatase (liver panel) if experiencing heptatoxicity symptoms

• ACC/AHA/ADA Guidelines: obtain ALT and AST at baseline (fasting ideal)

• Do NOT measure routinely if taking statin >3times ULN increase in transaminases with no symptoms does not occur frequently, does not impact occurrence, improves when decrease dose or give alternative statin

Statin Adverse effects/ interactions

• dyspepsia, increase blood glucose, myopathy/rhabdomyolysis (increased risk with gemfibrozil), CYP3A4 inhibitors (interaction)

what you draw when you have myalgia (myopathy/rhambdomyolysis)

CK (creatine kinase), CPK

Gemfibrozil myotoxicity

inhibits glucuronidation or preventing renal clearance of statins and increases statin levels, fenofibrate less potential to interfere with statin metabolism

hallmark of rhabdomyolysis

brown-tinged colored urine

risk factors for myotoxicity

older age, kidney/liver disease, excessive alcohol intake, heavy exercise

Not severe statin symtoms

rechallenge with modify dosing regimen, use another statin or in combo with nonstatin to obtain max lowering of LDL

True/False You measure CK levels routinely if taking statin

false— only take CK levels if severe statin-associated muscle symptoms

ACC/AHA/ADA 2018 Lipid Guidelines lipid panel

4-12 weeks after starting or adjusting statin dose then every 3-12 months

Foods to avoid with lovastatin, atorvastatin, simvastatin

grapefruit juice

If we double dose of statin does it double efficacy

No

Bempedoic Acid (Nexletol)

• adenosine triphosphate-citrate lyase (ACL) inhibitor

• decrease LDL-C by up regulating LDL receptors

• main effect: decrease LDL

Nexletol (Bempedoic Acid) indications

decrease MI and coronary revascularization risk in adults who are not able to take recommended statin and have CVD, or high risk for CVD event by do NOT have CVD

adverse effects Nexletol (Bempedoic Acid)

hyperuricemia, increased LFTs, tendon rupture

when to check lipid panel for Bempedoic Acid (Nexletol)

8-12 weeks after stating medication

Fibrates examples

gemfibrozil, fenofibrate

Fibrates MOA

• stimulate PPAR-a receptors

• increase HDL, decrease TG, increase apo A1 and A2

Class of Nexletol

ACL inhibitor

Adverse effects of Fibrates

gallstones- main,

Monitoring in Fibrates

CBC, LFTs

contraindications with Fibrates

gallbladder disease, hepatic disease, renal disease, primary biliary cirrhosis

Ezetimibe (Zetia)

• decrease LDL

• dose 10mg QD

adverse effects Ezetimibe (Zetia)

• increase LFTs, GI, back pain, chest pain, angioedema, gallstones, pancreatitis, ect.

• AVOID use with gemfibrozil

Main effect of Zetia

lower LDL

pathway Zetia works on

exogenous pathway

Nicotinic Acid- Niaspan

• decrease LDL and TG, decrease hepatic TG production

• DO NOT recommend dietary supplement SR products

• DO NOT recommend IR products

• NOT SUBSTITUTED FOR EQUIVALENT DOSES

• OTC fish oil: NOT FDA

• Niaspan: extended release—> safer profile, less hepatoxicity

Niaspan lipid effects

lower LDL, lower TG, increase HDL

Nicotinic Acid Adverse effects

• itching: prostaglandin mediated

• hyperuricemia

• hyperglycemia

• myopathy

• hepatoxicity (most with SR): max dose niaspan 2gm/day

• FLUSHING: prostaglandin mediated—> reduce with aspirin, Tylenol, take with food or bedtime, avoid hot shower

• rhabdomyolysis when dose ≥1gm/day and given with statin

Niaspan can activate

• peptic ulcers

Contraindications with Nicotinic Acid

• Active liver disease, active peptide ulcer disease, arterial bleeding

• Precautions(risk vs benefit)

  • Hx of liver disease

  • gout —> baseline uric acid levels repeat stabilized dose

  • DM (alternative to statins or vibrates) check baseline glucose level repeat when stabilized dose

Lomitapide (Juxtapid) main effect

Lower LDL

Lomitapide (Juxtapid)

approved for homozygous familial hypercholesterolemia

Boxed warning Lomitapide

• Increased liver transaminases (measure ALT,AST, alkaline phosphatase, total bilirubin at baseline; then at least ALT and AST before every dose increase or every month) for 1st year then at least ALT and AST at least every 3 months and before each dose increase

• increases hepatic fat

how is Juxtapid taken

orally

Where is Praluent stored

in fridge

Alirocumab (Praluent)

• PCSK9 inhibitor—binds to low-density lipoprotein receptors on hepatocyte surface to promote LDLR degradation within liver

• reduce risk of MI, stroke, and unstable angina requiring hospitalization in adults with CVD

Alirocumab (Praluent) dose

start at 75mg SubQ

Evolocumab (Repatha)

PCSK9 inhibitor

reduce risk of MI, stroke, and coronary revascularization in adults with CVD

SubQ

How is Leqvio used

SubQ

Fish Oil

• Increases LDL (5-10%), increases HDL (1-3%), DECREASE TG(30%)

Vascepa- Fish Oil

• EPA (omega 3 fatty acid)

• Dose- BID orally with good

• Hepatic impairment: monitoring LFTs

REDUCE-IT Trial

Patients had CVD or had DM and other CV risk factors: taking statin and fasting TG 135-499mg/dL and LDL 41-100mg/dL

Lovaza Fish Oil

• contains DHA and EPA

• oral administration

• GI upset effect

ACC AHA Guidelines

• Need to draw lipid profile within 24hours

• LDL accurate if TG are <400 (cannot calculate if TG >400)

LDL<70 mg/dL (calculation not reliable)

may measure direct LDL or modified LDL estimate to increase accuracy compared to calculation

High Intensity Statin (Lowering LDL by ≥50%)

Atorvastatin 40 or 80

Rosuvastatin 20 or 40

Moderate intensity statin (lowering LDL by 30-49%)

Low intensity statin (lowering LDL by <30%)

1st statin group

Secondary ASCVD prevention

Already high risk DONT need ASCVD score

2nd statin group

Severe hypercholesterolemia (LDL ≥ 190mg/dL)

Age 20-75

No risk score

3rd statin group

Primary prevention: adults 40-75 with DM and NO ASCVD and LDL ≥70mg/dL

4th statin group

Primary prevention: adults 40-75 and LDL 70-189 AND NO DM AND NO ASCVD AND ≥7.5% 10yr ASCVD risk

*NEED RISK SCORE

Clinical ASCVD defined

ACS, MI, stable or unstable angina or coronary or other arterial revascularization, stroke, TIA, PAD including aortic aneurysm

Very high-risk defined

multiple major ASCVD events OR 1 major ASCVD event and multiple high-risk conditions

≤75 YO with Clinical ASCVD

high intensity statin

Very high risk clinical ASCVD and on max tolerated statin dose and LDL ≥70mg/dL

adding ezetimibe

Clinical ASCVD and ≥75 YO

moderate or high-intensity statin

Primary Prevention: Severe Hypercholesterolemia

20-75 YO and LDL≥190mg/dL

high intensity statin/max tolerated statin (no risk assessment is needed, first goal: ≥50% LDL reduction)