27. Dyslipidemia Flashcards
TG > ____ can cause acute pancreatitis
> 500
Friedewald equation (LDL)
LDL = TC - HDL - (TG/5)
Do NOT use when TG > 400, can lead to falsely low LDL
Severe cholesterol elevations (including LDL ≥___ and TG ≥____) are very high risk and must be treated
LDL ≥ 190
TG ≥ 500
ASCVD risk is calculated using ___
Gender, age, race, smoking status
TC, HDL, LDL, statin use
BP, HTN med use
DM hx and aspirin use
Drugs that increase LDL and TG
Diuretics
Efavirenz
Immunosuppressants (e.g. cyclosporine, tacrolimus)
Atypical antipsychotics
Protease inhibitors
Drugs that increase LDL only
Fibrates
Fish oils (except Vascepa)
Drugs that increase TG only
IV lipid emulsions
propofol
clevidipine
bile acid sequestrants (~5%)
Conditions that increase cholesterol
Obesity, poor diet, alcohol use disorder, hypothyroidism, smoking, diabetes, renal/liver disease, nephrotic syndrome
ASCVD risk assessment should be repeated every ____ if low risk (<7.5%)
4-6 years
ASCVD risk score is not needed for pts with _____, as all pts in these groups should be started on a statin
clinical ASCVD, diabetes, or LDL≥190
Natural products for dyslipidemia
Red yeast rice (contains naturally occurring statin in varying amounts, can lower LDL)
OTC fish oils (can lower TG but increase LDL)
Garlic is no longer considered effective
Concern with cholesterol-lowering drugs and liver damage
Niacin, fibrates, potentially statins and ezetimibe may cause liver damage
Should not be used if AST or ALT is ≥ 3xULN
Statins MOA
inhibit HMG-CoA reductase, which prevents conversion of HMG-CoA to mevalonate
This is the rate-limiting step in cholesterol synthesis
Clinical ASCVD (CHD, stroke/TIA, PAD) - What intensity statin should be started in this patient?
High-intensity
Baseline LDL ≥190 - What intensity statin should be started in this patient?
High-intensity
DM and age 40-75 with LDL between 70-189 and multiple ASCVD risk factors - What intensity statin should be started in this patient?
High-intensity
DM and age 40-75 with LDL between 70-189 - What intensity statin should be started in this patient?
Moderate-intensity
Age 40-75 with LDL between 70-189 and ASCVD risk ≥20% - What intensity statin should be started in this patient?
high-intensity
Age 40-75 with LDL between 70-189 and ASCVD risk ≥ 7.5-19.9% + risk enhancing factors - What intensity statin should be started in this patient?
Moderate-intensity
High intensity statin options
Atorvastatin 40-80mg
Rosuvastatin 20-40mg
Moderate intensity statin options
Atorvastatin 10-20mg
Rosuvastatin 5-10mg
Simvastatin 20-40mg
Pravastatin 40-80mg
Lovastatin 40mg
Fluvastatin 40mg BID/80XL
Pitavastatin 1-3mg
Low-intensity statin options
Simvastatin 10mg
Pravastatin 10-20mg
Lovastatin 20mg
Fluvastatin 20-40mg
Statin equivalent doses
Pharmacists Rock At Saving Lives and Preventing Fatty deposits
Pitavastatin 2mg
Rosuvastatin 5mg
Atorvastatin 10mg
Simvastatin 20mg
Lovastatin 40mg
Pravastatin 40mg
Fluvastatin 80mg
Muscle damage from statins typically presents as muscle soreness, tiredness, or weakness that is symmetrical and occur within ___ of starting treatment (but can develop at any time)
6 weeks
Compare myalgias, myopathy, myositis, vs rhabdomyolysis
Myalgias = muscle scoreness and tenderness
Myopathy = muscle weakness ± CPK elevations
Myositis = muscle inflammation
Rhabdomyolysis = muscle symptoms with very high CPK (>10,000) plus muscle protein in the urin (myoglobinuria), which can lead to acute renal failure
How to reduce risk of myalgias in pts taking statins
avoid drug interactions, including OTC products
Do not use simvastatin 80mg/day
Do not use gemfibrozil + statin
If myalgias occur, what should you do?
Hold statin, check CPK, investigate other possible causes
After 2-4 weeks: rechallenge with same statin at same or lower dose
If myalgias return, discontinue statin. Once muscle symptoms resolve, use a low dose of a diff statin; gradually increase dose
Which statins are recommended to take in the evening?
Fluvastatin IR
Lovastatin IR take with evening meal
Lovastatin ER take at bedtime
Simvastatin
Contraindications for statins
Breastfeeding, liver disease, CYP3A4 inhibitors (with simvastatin and lovastatin), concurrent use of cyclosporine (with pitavastatin)
Warnings with statins
Muscle damage: myopathy/rhabdomyolysis with increased CPK ± acute renal failure
Higher risk with higher doses (e.g. simvastatin 80mg), advanced age, concurrent use of niacin, fibrates (e.g. gemfibrozil), or CYP3A4 inhibitors, hypothyroidism, renal impairment
Do not use during pregnancy for most pts (can consider for high risk CV events)
Diabetes: increased A1C/fasting BG; benefit of statin outweighs risk
When should lipid panel be checked after starting/changing dose of statin?
4-12 weeks after starting or changing dose and then annually
Which statins can you take any time of day?
Atorvastatin (Lipitor)
Rosuvastatin (Crestor)
Pitavastatin (Livalo)
Fluvastatin XL (Lescol XL)
Pravastatin (Pravachol)
Lipid effects of statins
Decrease LDL ~20-55%
Increase HDL ~5-15%
Decrease TG ~10-30%
In general, ____ and __ have less drug interactions compared to other statins
Rosuvastatin and pravastatin
Drug interactions with statins
CYP3A4 inhibitors
grapefruit
protease inhibitors
azole antifungals
cyclosporine
cobicistat
macrolides (except azithro)
amiodarone = limit max dose simvastatin 20mg/day/max, lovastatin 40mg/day
non-DHP CCBs = Amlodipine - Limit max dose simvastatin 10mg/day, lovastatin 20mg/day
Fibrates (gemfirbozil) and niacin can increase risk of myopathies and rhabdo
Add on therapies if statin is not enough
Ezetimibe and/or PCSK9 MAbs
If ezetimibe and/or PCKS9 MAbs are not enough: bempedoic acid (cholesterol synthesis inhibitor) and iclisiran (intracellular inhibitor of PCSK9 production)
In select populations, ___ and ___ are used to target high TG
Fish oils and fibrates
LDL threshold to add non-statin therapy for pt with clinical ASCVD and either very high risk or baseline LDL≥190
LDL ≥ 55
LDL threshold to add non-statin therapy for pt with clinical ASCVD not at very high risk
LDL ≥ 70
LDL threshold to add non-statin therapy for pt with no clinical ASCVD with DM and/or ASCVD Risk ≥ 20%
LDL ≥ 70
Ezetimibe MOA
inhibits absorption of cholesterol in small intestine
Side effects with ezetimibe (Zetia)
Myalgias
OtherS: Diarrhea, URTIs, arthralgias, pain in extremities, sinusitis
Lipid effects with Ezetimibe (Zetia)
Decrease LDL 18-23%
Increase HDL 1-3%
Decrease TG 5-10%
PCSK9 monoclonal antibodies (Alirocumab (Praluent), Evolucumab (Repatha)) MOA
block ability of PCSK9 to bind to LDL receptor, dramatically decrease LDL and reduce risk of CV revents
How are PCSK9 monoclonal antibodies (Alirocumab (Praluent), Evolucumab (Repatha)) administered?
SC once every 2 weeks of monthly
Lipid effects of PCSK9 monoclonal antibodies (Alirocumab (Praluent), Evolucumab (Repatha))
Decrease LDL~60%
Bile acid sequestrants (Colesevelam (Welchol), cholestyramine, colestipol) MOA
Bind bile acids in the intestine, excreted in feces
How should Colesevelam (Welchol) be taken?
with meal and liquid (comes as tabor granule packet)
sipping or holding suspension in mouth for prolonged periods may lead to tooth discoloration, erosion of enamel or decay - use good oral hygene
Statins are typically not recommended in pregnant patients. What cholesterol lowering medication is an option for pregnant pt?
Colesevelam (Welchol)
Colesevelam (Welchol) is also approved for ____
glycemic control in T2DM (decrease A1C by ~0.5%)
Lipid effects of Colesevelam (Welchol)
Lower LDL and increase HDL
but may increase TG ~5%
Colesevelam has fewer DDs compared to cholestyramine or colestipol. For cholestyramine or colestipol, take all other drugs at least ___ before or ___ after the bile acid sequestrants
1-4 hrs before
4-6 hrs after
Bile acid sequestrants can decrease absorption of which vitamins/supplements? Multivitamin may be needed but separate from bile acid sequestrant.
Vitamin A, D, E, K
Folate
Iron
The following meds should be taken 4 hrs prior to colesevelam ___
levothyroxine
Others: cyclosporine, glimepiride, glipizide, glyburide, olmesartan, phenytoin, and oral contraceptives containing ethinyl estradiol and norethindrone
Fibrates (Fenofibrate, gemfibrozil) MOA
PPAR alpha activators which upregulate expression of apoC-II and apoA-I. ApoC-II increases lipoprotein lipase acitivity»_space; catabolism of VLDL particles»_space; decrease TG significantly but can lead to increased LDL in the setting of very hihg TG
Which formulations of fenofibrate should be taken with emals?
Fenoglide, lipofen
Contraindications of fibrates
Sever eliver disease, including primary biliary cirrhosis, gallbladder disease
Others: severe renal disease CrCl ≤30, breastfeeding, concurrent use with repaglinide or simvastatin (gemfibrozil only)
Warnings for fibrates
Myopathy, increased risk when coadministered with statin - particularly in the elderly, DM, renal failure, hypothyroidism), cholelithiasis, reversible increase SCr (2mg/dL)
Side effects of fibrates
Dyspepsia (gemfibrrozil)
Increased LFTs
Which fibrates should not be given with ezetimibe or statins?
Gemfibrozil
Fibrates can increase the effects of ___ and ___
sulfonylrueas and warfarin
Niacin MOA
decrease the rate of hepatic synthesis of VLDL (decrease TG) and LDL
(Does not take up HDL particle»_space; HDL increases)
Niacin is also known as ___
nicotinic acid or vit B3
Administration notes for niacin
Titrate slowly
IR: with food
ER: at bedtime after low-fat snack
CR/SR: with food
Warnings for niacin
Rhabdomyolysis with niacin doses ≥1g/day combined with statins
Hepatotoxicity
Increased BG, uric acid, decreased phosphate
Side effects for niacin
Flushing, pruritus (itching), vomiting, diarrhea, increased BG, hyperuricemia (gout)
Others: nausea, cough, orthostatic hypotension, hypophosphatemia, decreased platelets
IR niacin has poor tolerability d/t ___
flushing/itching
CR/SR niacin has less (but still significant) flushing but more ___
hepatotoxicity
ER niacin is preferred d/t less ____ but it is most expensive
flushing and hepatotoxicity
How to reduce flushing with niacin?
Take aspirin 325mg (or ibuprofen 200mg) 30-60min before the dose; take with food but avoid spicy food, alcohol and hot beverages (Which can worsen flushing)
T/F: Formulations of niacin are interchangeable
False
Lipid effects of Niacin
Increased HDL
Take niacin ___ after bile acid sequestrants
4-6hrs
Fish oils are indicated as an adjunct to diet when TG ≥ ___
500
Which fish oil product is recommended for ASCVD risk reduction
Icosapent ethyl (Vascepa)
When using fish oils, use caution in pts with known hypersensivity to ____
fish and/or shellfish
What are fish oil products used to lower TG?
Omega-3 cid ethyl esters (Lovaza)
Icosapent ethyl (Vascepa)
Side effects of fish oils
Eructation (burping), dyspepsia, taste perversion (Lovaza), arthralgias (Vascepa)
Lipid effects of fish oils
Lowers TG up to 45%
Can increase LDL (up to 44% with Lovaza, no increase seen with Vascepa)
Concern with fish oil use and surgery/warfarin use
Fish oils can prolong bleeding time
Monitor INR if pts are taking warfarin
MOA of iclisiran (Leqvio)
Inhibits intracellular production of PCSK9
Can be considered as alt add-on treatment to maximally tolerated statin in pts with poor adherence or an inability to tolerate PCSK9 MAb
