Cardiovascular Module Exam 1 Therapeutics of Dyslipidemia (Baker)

define primary prevention

aims to keep an individual at risk of heart disease from having a first heart attack or stroke

define secondary prevention

· efforts started after someone has had a stroke or heart attack to prevent a 2nd event , halt progression of heart disease, or prevent early death

what are desirable TC (total cholesterol) levels

<200mg/dl

what are desirable LDL-C levels

< 100mg/dL

when is lipid screening recommended and how often

· It is recommended that beginning at 19 years old and at least every 5 years, a lipid profile is recommended

o More frequent screening for people with additional ASCVD risk factors

when is lipid screening recommended for people with a 1st or 2nd degree relative with premate ASCVD, severe hypercholesterolemia, or FH

a single lipid profile can start at 2 years old to identify Familia Hypercholestermia

what are the names of the 2 equations to calculate LDL-C

Martin and Sampson equations

describe ApoB

o Directly quantifies the # of atherogenic lipoproteins

o More accurate measure of atherogenic particle burden than LDL-C

describe Lp(a)

o LDL-C-like-particle, structurally distinct from LDL

o Carries a single apoprotein (a) strand bound to its apoB-100 component

describe Lp(a) concentration recommendations

should be measured at least once for ASCVD risk-assessment

what are teh 4 steps for CPR Risk Evaluation for Dyslipidemia

1. calculate ASCVD risk

2. Personalize

3. Reclassify and Reassess

4. Decide and treat

describe Step 1 (calculate ASCVD risk)

· Adults 30-79 years old without ASCVD or subclinical atherosclerosis and with LDL-C between 70-189 mg/dL

o PREVENT calculator should be used to assess 10-year ASCVD risk

what is defined as low 10-year ASCVD risk

<3%

what is defined as borderline 10-year ASCVD risk

3- <5%

what is defined as intermediate 10-year ASCVD risk

5- <10%

what is defined as high 10-year ASCVD risk

>/= 10%

describe Step 2 (personalize) step of risk evaluation

Look at risk enhancers for those with borderline (3-5%) 10-year ASCVD risk

describe step 3 (reclassify and reassess) step of risk evaluation

· If clinical or patient uncertainty, consider calculating a CAC score and revise results

what does a Coronary Calcium (CAC) Score tell you

it tells you how much calcium deposit is present in the coronary arteries as a score

describe step 4 (decide and treat) of risk evaluation

· Lifestyle recommendations are recommended for all risk levels

· lipid-lowering therapies are reserved for intermediate, high, and sometimes borderline risk patients

describe lifestyle changes to prevent dyslipidemia

o Diet, exercise, maintenance of healthy weight, healthy sleep, stress management, avoidance of tobacco products

describe dietary management of LDL-C disorders

o Eat fruits, veggies, nuts, legumes, whole grains, fiber

o Replace saturated and trans fats with dietary monounsaturated and polyunsaturated fats

dietary supplement recommendation in dyslipidemia

not recommended in place of prescription therapy to lower TG or LDL-C

name the 2 hydrophilic statins

pravastatin and rosuvastatin (the rest are lipophilic)

what are some questions to ask when starting a statin?

· Do they have ASCVD (primary. Vs. secondary prevention)

· What are their comorbidities?

· Hat is their fasting serum LDL-C level?

· What is their age?

· What is their 10-year (and maybe 30-year) ASCVD risk?

what are the 3 main groups we are concerned about for primary prevention of ASCVD

o Adults 30-79 y/o, LDL-C 70-189 mg/dL

o Severe hypercholesterolemia: LDL-C >/= 190 mg/dL

o Diabetes without established ASCVD

recommendation for primary prevention of ASCVD in adults with diabetes (regardless of LDL-C) and 20-39 years old

o moderate-intensity statin if DM-specific risk enhancers (like long duration of DM, bad kidneys/eyes)

o If otherwise healthy, not a need to be put on statin always

recommendation for primary prevention of ASCVD in adults with diabetes (regardless of LDL-C) and 40-75 years old + LDL goal

moderate-intensity statin (high-intensity if multiple ASCVD risk factors)

o LDL-C goal <100mg/dL (<70 mg/dL if multiple ASCVD risk/high intensity)

recommendation for primary prevention of ASCVD in adults with severe hypercholesterolemia (LDL-C >/= 190mg/dL) and LDL goal

o Maximally tolerated statin (high intensity unless not tolerable)

o LDL-C goal <70 mg/dL if high or <100mg/dL if moderate

what is considered severe hypercholesterolemia

LDL-C >/= 190 mg/dL

LDL goal for most moderate-intensity statins

<100mg/dL

LDL goal for most high-intensity statins

recommendation for primary prevention of ASCVD in adults (30-79 years old) with LDL-C 70-189mg/dL with an intermediate 10-year risk

(5-10% 10 year risk)

§ Moderate-high intensity statin

§ LDL-C goal <100mg/dL

recommendation for primary prevention of ASCVD in adults (30-79 years old) with LDL-C 70-189mg/dL with a high 10-year risk

High (>10% 10 year risk)

§ High intensity statin

§ LDL-C goal <70 mg/dL

how much do high-intensity statins reduce LDL-C by

50%+

define high-intensity atorvastatin dose

(40mg) 80mg

define high-intensity rosuvastatin dose

20mg (40mg)

what are the 2 high-intensity statin doses

o Atorvastatin (40mg) 80mg

o Rosuvastatin 20 mg (40mg)

what are 4 examples of major ASCVD events

o ACS within the past 12 months

o History of MI (other than ACS above)

o History of ischemic stroke

o Symptomatic PAD

what are some high risk conditions for ASCVD

o Age >/=65 years old

o Coronary bypass or percutaneous intervention

o Current smoker

o Diabetes

o H/o CHF

o HTN

o LDL-C >/= 100mg/dL despite maximally tolerated statin + ezetimibe

what is considered "high risk" for secondary ASCVD prevention

1 major ASCVD event

what is considered "very high risk" for ASCVD prevention

o 2+ major ASCVD events

o OR 1 major ASCVD event and 2+ high-risk conditions

what is recommended for secondary prevention in high risk patients and what is the LDL goal

start a high-intensity statin or max tolerated

goal of LDL-C <70mg/dL

hat is recommended for secondary prevention in VERY high risk patients and what is the LDL goa

start a high-intensity statin or max tolerated

goal of LDL-C <55mg/dL

whe should follow-up on lipid levels be done initially and after?

4-12 weeks after initiation and then every 6-12 months

what are the 3 short half-life statins? when should they be dosed?

fluvastatin, pravastatin, and simvastatin

they should be given at bedtime/evening

what are the 3 longer half-life stats? when should they be dosed?

rosuvastatin, atorvastatin, and pitavastatin

they can be given at any time of day

which statin should be given with food to increase bioavailability

lovastatin

lovastatin dosing instructions

Take with dinner for most food with least fiber

statin ADE's of concern

o Statin-attributed muscle symptoms (SAMS)

o Elevated hepatic transaminases

o Increased risk of new-onset type 2 diabetes

statin contraindications

o Unstable/acute liver disease

o Pregnancy (can be used in highest-risk patients)

o Nursing mothers

what is SAMS

it is statin-attributed muscle symptoms that can occur with statins (especially lipophilic ones)

define myalgia

unexplained muscle achiness or soreness, often without CK elevation

define myopathy

muscle "weakness" and sometimes associated with CK elevation

define myositis

muscle inflammation confirmed by muscle biopsy

define rhabdomyolysis

· CK elevation 10 ULN with myoglobinuria or acute kidney failure (rare)

o CK indicated if rhabdomyolysis is suspected

what are some risk factors for SAMS (Statin-attributed muscle symptoms)

o Age 65+

o Low BMI

o Obese

o Female

o Hypothyroidism

o DM

o CKD/ chronic liver disease

o Alcohol consumption

o High-dose statin therapy

o Pharmacotherapy affecting statin metabolism

what are some ways to help reduce SAMS

o Decrease statin dose

o Temporarily hold statin

o Change to another statin (hydro v. lipophilic)

o Alternative dosing (every other day)

which 2 therapies are unlikely to be helpful in SAMS

o CoQ10 supplementation

o Routine CK monitoring

describe how SAMS presents

· New-onset bilateral, symmetrical, proximal muscle pain/weakness

· Occurs within weeks after the initiation or increased statin dosing

· Symptoms typically resolve within a similar period after stopping the statin

· May recur upon reinitiation

describe elevated LFT's with statins

o Usually transient and resolve with time

o Obtain LFT's at baseline

o Can repeat LFTs after initiation and dose increases

o Routine LFT monitoring NOT recommended

describe the increased risk of new-onset T2DM with statins

o Dose-dependent

o More likely in those with risk factors for diabetes

o Not associated with hyperglycemia

o Benefits of statins outweigh risks

can you give statins to patients with elevated ASCVD risk with chronic, stable liver disease or elevated diavetes risk or new-onset diabetes?

yes! risk v. benefit

what do DDI's with statins increase the risk for

SAMS

what are 2 major CYPs inhibitions interfere with statin oxidation

CYP3A4 and CYP2C9

which 3 statins have significant CYP3A4 metabolism?

lovastatin, simvastatin, (less atorvastatin)

which drugs should you limit the dose of lovastatin & simvastatin (CYP3A4 metabolism) with?

amiodarone, amlodipine, conivaptan, diltiazem, dronedarone, gemfibrozil, verapamil

which 3 statins have significant CYP2C9 metabolism?

fluvastatin, pitavastatin, rosuvastatin

which drug should you monitor with fluvastatin, pitavastatin, and rosuvastatin (CYP2C9 metabolism)

colchicine

which drug should you avoid with ALL statins? why?

gemfibrozil due to increased risk of SAMS

how should statin therapy be intensified in patients with no ASCVD and LDL >100mg/dL

add ezetimibe, a PCSK9 mAb, and/or bempedoic acid

how should statin therapy be intensified in patients with ASCVD and what is the LDL goal

§ Add ezetimibe, a PCSK9 mAb, and/or bempedoic acid

§ Goal should be LDL-C < 55mg/dL

how should statin therapy be intensified in patients with diabetes (ages 40-75) and what is the LDL goal (s)

o if not achieving LDL-C <100 mg/dL or <70 mg/dL with multiple risk factors

§ add ezetimibe and/or bempedoic acid or a PCSK9 mAB

how should statin therapy be intensified in patients with a high 10-year risk (10%+) and what is the LDL goal

1. if LDL-C not <70mg/dL--> add ezetimibe

2. if still not controlled: add PCSK9 mAB or bempedoic acid

how should statin therapy be intensified in patients with clinical ASCVD and a VERY high risk and what is the LDL goal

treatment goal is LDL-C <55mg/dL

§ if goal not achieved, add ezetimibe and/or PCSK9 mAB

§ if unable to tolerate, obtain, or adhere to PCSK9 mAB then start inclisiran

§ if goal still not achieved, then add bempedoic acid

how should statin therapy be intensified in patients with clinical ASCVD and NOT a very high risk and what is the LDL goal

treatment goal is LDL-C <70mg/dL

§ if goal not achieved, add ezetimibe, PCSK9 mAB, and/or bempedoic acid

§ if unable to tolerate, obtain, or adhere to PCSK9 then start inclisiran

ezetimibe brand name

zetia

what is unique about ezetimibe and its side effects

it's not systemically absorbed --> only GI ADEs

contraindications of ezetimibe

active liver disease and unexplained persistent LFT inc.

DDI's of ezetimibe

Fibrates and cyclosporine increase ezetimibe concentration

inclisiran dosing consideration

o Administered by a healthcare professional

enlicitide dosing

PO QD on ab empty stomach

when is bempedoic acid indicated

reducing CV event risk in those who are unable to take statins

ADE's of bempedoic acid

URTI, increase in uric acid (warning), tendon rupture (warning), muscle spasms

what are the 2 warnings with bempedoic acid

uric acid and tendon rupture

what should bempedoic acid be avoided with

simvastatin > 20mg/day or pravastatin >40mg/day

cholestyramine brand name

prevalite

colestipol brand name

colestid

colesevelam brand name

welchol

when to use bile acid sequestrants?

in pregnancy (due to lack of systemic absorption) if hypercholesterolemia but without hypertriglyceridemia

ADE's of bile acid sequestrants

· all GI, abdominal pain, bloating, dyspepsia, N, constipation

o Powder has an unpleasant mouth feel

o Tablets are geerally more tolerated

o may increase TG's

when should bile acid sequestrants not be used and why?

if TG > 300mg/dL because it can increase TG levels

which drugs can have DDI's with bile acid sequestrants? what should be done to stop this?

o Low bioavailability of drugs: warfarin, theophylline, digoxin, levothyroxine

o Administer at least 1-2 hours before or 4 hours after other medications

dosing of colestyramine

o powder packet

o Initially take BID then maintenance increase dose BID with meals

dosing of colesevelam

o Tablet and packet

o Dosed as 6 tabs/day or one packet a day with meals and liquid

dosing of colestipol

o Tabet and packets/granules

o Dosed BID or QD

what TG levels can cause pancreatitis risks

TG > 1000 mg/dL

what TG levels are considered normal

TG < 150 mg/dL

conditions that can be secondary causes of hypertriglyceridemia

o Poorly controlled DM

o Alcohol abuse/excess

o CKD

o Uncontrolled hypothyroidism

o Cushing syndrome

o Rheumatoid arthritis

o Psoriasis

o Systemic lupus erythematosus

medications that can be secondary causes of hypertriglyceridemia

o Protease inhibitors

o Cyclosporine

o Beta-blockers

o Diuretics

o Estrogen

o Steroids

o Bile acid sequestrants

o Antipsychotics

o Isotretinoin