Anti-hyperlipidemics Flashcards
Dyslipidemia risks
-coronary, cerebrovasc, peripheral arterial disease
-major risk for CHD
-coronary artherosclerosis contributes to ischemic heart disease
Lipids
-cholesterol
-cholesterol esters
-TGs
-phospholipids
Lipoproteins
-LDL
-HDL
-VLDL
Apolipoproteins
-Apo-B
-Apo-A1
-Apo-CIII
Artherosclerosis pathogenesis
- endothelial injury
- inflammatory response
- Macrophage infiltration
- Platelet adhesion
- Smooth muscle cell proliferation
- Extracellular matrix accumulation
Dyslipidemia sx
-MOST ASYMPTOMATIC
-depends on severity and duration of disease
-chest pain
-palpitations
-sweating
-anxiety
-SOB
-loss of consciousness
-difficulty w speech or movement
-ab paain
-sudden death
Signs of dyslipidemia
-pancreatitis
-eruptive xanthomas
-peripheral polyneuropathy
-inc BO
-waist size (>40 inches men >35 women)
-BMI >30kg/m
Dyslipidemia lab values
-inc Non HDL-C, TC, LDL-C
-inc TGs, APO-B, CRP, LDL-P
-DEC HDL
LDL-C
-amount of cholesterol in LDL particles
LDL-P
-number of LDL particles
-not routinely ordered
Non HDL-C
-amount of cholesterol in atherogenic particles
-not routine
-non-HDL-C = TC- HDL
Apo-B
-number of artherogenic particles
-not routine
ApoB, LDL-P, non HDL-C
-all valid in non-fasting sample w elevated TGs
-all mosre predictive of future CVD risk than LDL-C alone
Non-fasting lipid profile appropriate if:
-assessing initial risk
-pt not on lipid therapy
-no family hx of genetic hyperlipidemia
-pt TGs low
Fasting Lipid Panel (FLP)
-TC
-TG
-HDL-C
-LDL-C (friedewald equation)
Friedewald equation
-estimate LDL from FLP
-LDL calculation not valid when TG >400
-LDL = TC - HDL - TG/5
What else is important w a FLP
-Non-fasting sample (TC, HDL)
-TC/HDL (goal <5:1, optimal 3-3.5:1)
pracice FLP
practice FLP
Nonpharma tx
-DASH diet (veggiess, fruit, grain, fish, legumes, oils, nuts)
-reduce calories from saturated and trans fats (5-6% of calories)
-lower sodium intake to at least 1000mg/day
-exercise 90-150min/week
Saturated Fat intake calculation
-9 cal per gram of fat
-19g fat *9 = 171 cal
-171/2000 = 8.6%
-double quarter pounder w cheese
-goal 5-6%
Olestra to Reduce intake of saturated fats and cholesterol
-nondigestable, nonabsorbable, noncaloric fat substitute
Soluble fiber
-oat bran
-pectins or gums
-psyllium products
-binds cholesterol in gut and reduces hepatic production and clearance
-psyllium seed 10-15g daily may dec TC and LDL by 20%
Psyllium products
-binds cholesterol in gut and reduces hepatic production and clearnace
-psyllium seed 10-15g daily may dec TC and LDL by 20%
Lifestyle change
-Olestra
-soluble fiber
-plant stanols and sterols
-weight reduction (10% loss if overweight)
-inc physical activity 40 min daily 3-4 days a week
-smoking cessations
Omega-3 Fatty Acids
-eating fish once weekly can reduce CV risk
-EPA/DHA
-reduces TG
-may increase LDL 4-49%
-most products OTC
-Lovaza
-Vascepa
-harder to stop bleeding (SSRIs too)
-NOT GOOD FOR AFIB
Lovaza
-2-4g qd or divided BID
-omega-3
Vascepa
-2g BID wf
-omega-3
-icosapent ethyl (IPE): the only triglyceride
-risk-based nonstatin therapy FDA-approved for ASCVD risk reduction
Effects of non-pharma therapy
-reducing saturated fat and adding 2g plant sterols great
Pharmacologic treatment options
-HMG-CoA reductase inhibitors (statins)
-Bile acid resins/sequestrants
-Niacin
-Cholesterol absorption inhibitor
-fibrates
-PCSK9 inhibitors/monoclonal antibodies
-Inclisiran
-Bempedoic acid
Pharma agents that have more effect on TGs
-fibrates
-omega-3
HMG-CoA reductase inhibitors
-lovastatin (altoprev, mevacor)
-pravastatin (pracachol)
-pitavastatin (livalo)
-simvastatin (Zocor)
-fluvastatin (lescol
-atorvastatin (lipitor)
-Rosuvastatin (crestor)
Low intensity statins + doses
-simvastatin 10mg
-pravastatin 10-20mg
-lovastatin 20mg
-fluvastatin 20-40mg
Moderate intensity statins
-atorvastatin 10-20mg
-rosuvastatin 5-10mg
-simvastatin 20-40mg
-pravastatin 40-80mg
-lovastatin 40-80mg
-fluvastatin 40mg BID
-fluvastatin XL 80mg
-pitavastatin 1-4mg
High intensity statins**
-atorvastatin 40-80mg
-rosuvastatin 20-40mg
Fluvastatin (lescol) properties
-CYP2C9
-lipophillic
-minimal effect on food absorption
-admin IR in evening, XR whenever
Pitavastatin properties
-CYP2C9,2C8
-lipohillic
-dec food absorption
-admin whenever
Pravastatin properties
-hydrophillic
-dec food absorption
-admin whenever
Lovastatin properties
-CYP3A4
-lipophillic
-inc food absorption
-IR evening, XR any time
Simvastatin properties
-CYP3A4,3A5
-lipophillic
-no effect on food
-take whenever
-Atorvastatin properties
-CYP3A4
-lipophillic
-no effect on food
-take anytime
Rosuvastatin properties
-CYP2C9
-hydrophillic
-no effect on food
-take anytime
Lipophillic statins
-fluvastatin
-pitavastatin
-lovastatin
-simvastatin
-atorvastatin
-more likely for muscle pain
hydrophillic statins
-pravastatin
-rosuvastatin
-inc risk of liver toxicity
statins w CYP3A4 interactions
-lovastatin
-simvastatin
-atorvastatin
When to take simvastatin
-evening
simvastatin 80mg
-lets not use that in practice
-inc adverse effects
Statin considerations
-well tolerated
-LFT
-muscle toxicity (myopathy/rhabdomyolysis)
-muscle pain
-dark urine
-avoid lots of grapefruit juice
-AVOID in pregnancy and ppl that might get pregnant
Statin LFT monitoring
-obtain LFT at baseline
-repeat if clinically indicated
-dc if LFTs 3x upper limit of normal
-LFT in the 1000s
Statin adverse effects
-impaired renal/hepatic function
-prior statin intolerance
-muscle disorders
-unexplained ALT elevations >3 x normal (1000s)
-other drugs
-over 75 years old
What to do when pt experiences muscle symtpom/fatigue
-dc statin and evaluate for rhabdomylosis
-evaluate exacerbating conditions
-restart or lower dose once sx resolve
-most times go from lipophilic to hydrophillic
statin contraindications
-liver disease
-elevated transaminases
-preg/breastfeeding
statin and muscle injury incidence
-not that high tbh
-check CK >10x upper limit, dc statin
-might need to switch to non CYP3A4
-one glass of grapefruit juice prob not gonna effect anything tho
-consider CoQ10 150-200mg qd prior to statin rechallenge and during therapy
statin muscle injury management
-assess if exercise related
-dc and see if resolves
-switch to hydrophillic statin
-change dose
-consider other agents
Statin alt dosing strategy
-every other day or once weekly can help and dec cost
-double daily dose if every other day
Simvastatin contraindications*
-itraconazole
-ketoconazole
-posaconazole
-erythromycin
-clarithromycin
-telithromycin
-HIV protease inhibitors
-nefazodone
-gemfibrozil
-cyclosporine
-danazol
->10mg: verapamil and diltiazem
->20mg: amiodarone, amlodipine, ranolazine
statins and hyperglycemia
-start statin anyway
-be aware of hyperglycemia risks
statin monitoring
-FLP at baseline
-FLP 4-12 wekks after initiation
-FLP 3-12 months as indicated
-consider CK if risk of muscle probs
-CK if muscle sx
-hepatic function in s/sx hepatotoxicity
Bile Acid Resins (BARs) drugs
-cholestyramine (questran, prevalite)
-Colestipol (colestid)
-Colesevelam (welchol)
Bile Acid Resin mech
-cation exchange resins
-traps bile and excretes it
-no bile = body makes more bile using cholesterol
BAR disadvantages
-may inc TGs
-take other meds 1 hour before or 4 hours after
BAR adverse effects
-GI (Nausea, constipation, flatuelence, bloating)
-impaired absorption of fat soluble vitamins (ADEK)
-hypernatremia
-hyperchoresmia
-GI obstruction
BAR might dec activity of
-acetaminophen
-TZDs
-warfarin*
-digoxin*
-contraceptives
-steroids
-ezetimibe
-fibrates
-thiazide diuretics
BAR contraindications
-cholestyramine: bilary obstruction
-colesevelam: hx bowel obstruction, TGs >500 or hx of hyperTG-induced pancreatitis
Niacin
-OTC
-CV benefits
-not regulated well
-hepatotoxicity risk
Niacin flushing
-prostaglandin
-admin ASA 325mg 30 min before niacin
-take closer to meals
-avoid alc
-start lower doses
-inc LFTs
-hyperuricemia and hyperglycemia
-may inc levels of statins
Niacin contraindications
-hepatic disease
-transaminase elevations
-peptic ulcer
-arterial hemorrhage
Ezetimibe (Zetia) mech
-cholesterol absorption inhibitor
-combo w simvastatin = Vytorin
-can dec LDL 12-20% more as combo
Exetimibe adverse effects
-fatigue
-diarrhea
-GI upset
-well tolerated
Ezetimibe contraindications
-use w statin and active hepatic disease or transaminase elevations
-preg/breastfeeding
Fibrate drugs
-fib
-more for TG instead of LDL
fibrate side effects
-GI
-rash
-myalgia
-dizziness
fibrate contraindications
-hx gallbladder
-ERSD or dialysis
-persistent liver disease
fibrates inc levels of
-statins (dont give both)
-ezetimibe
-sulfonylureas
-warfarin
PCSK9 monoclonal antibody drugs
-Alirocumab (praluent)
-Evolocumab (repatha)
PCSK9 mech
-inhibits PSCK9 binding to LDL receptors and upregulate recycling of LDL receptors
-43-64% reduction in LDL
PSCK9 indication
-adj to diet and statin
-HeFH or ASCVD
PSCK9 adverse effects
-GI upset
-inc LFTs
-inj site reaction
-myalgia
-influenza
PCSK9 consider for:
-stable and progressive ASCVD
-high risk/statin intolerant
-smth else
Inclisiran (Leqvio)
-dec LDL and cholesterol
-inj
-approved for adults only (unlike PCSK9)
Inclisiran indication
-adj to diet
-HeFH or ASCVD
Inclisiran mech
-siRNA
-inhibits translocation of PCSK9 inhibiting PCSK9 production
-prolongs activity of LDL receptors
Inclisiran adverse effects
-inj site rx
-arthralgia
-UTI
-diarrhea
-bronchitis
-pain in extremities
-dyspnea
Inclisiran dosing
-initial dose + one at 3 months
-then twice a year
Bempedoic Acid (nexletol) use
-not seen
-adj to diet and statin
-reduce LDL in HeFH or ASCVD
Bempedoic acid adverse reaction
-URTI
-muscle spasms
-hyperuricemia
-back/ab pain
-bronchitis
-anemia
-elevated liver enzymes
Bempedoic acid cautions
-may inc blood uric acid levels and lead to gout
-risk tendon rupture
-avoid use w simvastatin > 20mg and pravastatin >40mg (myopathy)
Bempedoic trials
-reduce risk of MI
Red yeast rice
-lovastatin ingredient
-shown to lower TC LDL TG
-maybe inc HDL
-same effects/interaction as statins
-no regulation or guidelines for use
Lomitapide (Juxtapid)
-HoFH
-only available through REMS
-boxed warning for hepatotoxicity
Evinacumab (Evkeeza)
-mab for HoFH
-IV infusion q4weeks
Guideline risk groups
-clinical ASCVD (cardiovasc event)
-diabetes 45-75y/o
-LDL>190
-over 75y/o
-ASCVD risk >20%
Primary prevention groups
-pt w no ASCVD event
-hypercholesterolemia
-DM
-over 75
primary prevention if LDL-C >190mg
-no risk assessment
-high intensity statin (class I)
-moderate if over 75
primary prevention in DM age 40-75
-moderate intensity statin
-risk assessment to consider high-intensity
age >75 primary prevention
-clinical assessment
-discuss risks
-moderate dont really go high
primary prevention in ASCVD >20% under 75 y/o
-always high intensity
guideline slide
risk enhancing factors for primary prevention
-fam hx of premature ASCVD
-LDL > 160 constitently
-CKD
-TG > 175
-pre-eclampsia
-premature menopause
-inflammatory disease
-ethnicity
-metabolic syndrome
-ApoB,CRP,Lp labs high
-decreased ankle-brachial index
Secondary prevention eligibility
-past ASCVD event
-MI
-angina (stable or unstable)
-revascularization
-stroke (TIA)
-Peripheral Artery Disease (incl aortic aneurysm)
Secondary prevention
-always high intensity statin
-mod if over 75
-add zetia if too high
-then go PSCK9 inhibitor
Patients benefiting from statin
-clinical ASCVD at any age
-LDLC>190
-40-75 w DM or ASCVD risk
-fam hx
-risk discussion everyone else
Statin monitoring
-initiate statin
-follow up 4-12 weeks until dose stable
-follow up every 3-12 months
Coronary Artery Calcium test (CAC)
-not used often
-measures calcium buildup
-use if risk decision still unclear to use statin
-CAC=0: assess other risks
-CAC=1-99: FAVORS statin therapy esp over 55y/o
-CAC>100: initiate at least mod statin
patient groups considered for non-statin therapy
-under 75 on statin for seconday prevention
-over 21 on statin for primary prevention
-40-75 w DM for primary prevention
when to treat non-statin for secondary prevention under 75
-w or w/o additional risk factors
-LDL-C threshold of 70mg/dl on max statin
-consider PSCK9 if veery high risk and LDL not at goal
when to treat non-statin over 21 for primary prevention
-baseline LDL>190 no underlying causes
-add ezetimibe if reduction <50% or LDL > 100
when to treat non-statin age 40-75 w DM for primary prevention
-risk assessment
-ezetimibe if ASCVD risk >20% on max statin
non-statin recommendations after max statin
- ezetimibe if LDL not at goal or pt w DM w ASCVD risk >20%
- PSCK9 inhibitors consider if LDL not at goal or if pt cannot tolerate statin/ezetimibe
other: BAS if <50% reduction in LDL on max statin + ezetimibe and TG>300
Treatment goals
-treat to target
-primary: LDL < 100
-secondary: LDL<70
-or max tolerated for ease
should tx be expanded?
-meds dont reverse damage
-may be beneficial to use in younger adults
-still being looked at for long-term efficacy
Hypertriglyceridemia categories
-persistent
-moderate (150-499)
-severe (>500)
-pt w DM have hyperTGs w high A1c (turns extra sugar into TGs)
persistent hyper TG
-fasting TG >150 after 4-12 weeks lifestyle intervention, stable dose of max statin, and secondary cause evaluation
moderate hyper TG
-excess TGs carried in VLDL
-150-499
Severe hyperTG
> 500
-excess TGs in VLDLs
-elevated chylomicrons inc pancreatitis risk
-high pancreatitis risk
HyperTG treatment
-give statin
Secondary TG factors
-obesity
-metabolic syndrom
-alc use
-DM
-HYPOthyroidism
-liver/kidney disease
-meds (slide102)
lifestyle mods to tx hyperTGs
-5-10% weight loss = 20% dec in TG
-low fat diet
-restrict alc, sugar, refined carbs
-physical activity
Pharma tx of hyperTGs
-use statin
-adults 40-75 w mod-severe TGs and ASCVD risk >7.5% = statin
-add fibrate OR omega-3 FA in severe esp if TGs>1000 and max out statin (vascepa or lovazza first)
patient cases
