dyslipidemia clinical case based approach · 2020. 12. 8. · dmt2
TRANSCRIPT
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Dyslipidemia
clinical case based
approach
Dr Tooba kazemi
Professor of cardiology
Dr Maryam rezaie
Assistant Professor of
endocrinology
Dr Shima jafari
Assistant professor of
clinical pharmacy
2020
In the name of God
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Dyslipidemia Definition
Dyslipidemia isDisorder in lipoprotein metabolism
Defined as elevated total cholesterol , LDL, TG or low levels of HDL
An important risk factor for coronary heart disease (CAD) and stroke
HLP / DLP ?
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Importance of Dyslipidemia
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Lipid level CAD risk
Each 1%
increase in LDL
1% increase in the risk of CHD
in women and men
Each 1%
increase in Non-HDL-C
1% increase in the risk of CHD
in women and men
Each 89 mg/dL
increase in TG
37% increase in the risk of CVD in women
14% increased risk in men
Each 1 mg/dL
increase in HDL-C
2% decrease in CVD death in men
3% decrease in CVD death in women
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Prevalence of DLP in Our Studies
http://jrhs.umsha.ac.ir/index.php/JRHS/article/view/2513/
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Sign and Symptom
No symptoms
Symptomatic vascular
disease: CAD, Stroke, PAD
Acute pancreatitis
No sign
may be Xanthoma
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Etiology
PRIMARY
SECONDARY
PRIMARY
Genetic
Hypercholesterolemia
Hypertriglyceridemia
Combination of
Hypercholesterolemia and
Hypertriglyceridemia
8
SECONDARY
Life style :
• Diet
• Lack of exercise
• Smoking
• Stress
• Excessive alcohol intake
Diseases
Drugs
Obesity
SECONDARY
Diseases
• Diabetes mellitus
• Nephrotic syndrome
• Renal failure
• Hypothyroidism
• Cholestasis
Drugs
• Thiazide diuretics
• β-adrenergic blockers
• Oral contraceptives
• Corticosteroids
• Isotretinoin (vitamin A
derivative)
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Standard serum lipid profile measurement: CHOL, HDL ,TG
LDl estimate by of LDL Friedewald equation.
LDL=Chol –(VLDL + HDL)
VLDL=𝑇𝐺
5
LDL=Chol –(𝑇𝐺
5+ HDL)
Error in Friedewald formula
1. Nonvalid in TG≥400mg/dl
2. Error is in LDL <70mg/dl
Fasting or non Fastig :
Small, clinically insignificant differences in Chol ,HDL in fasting or non-fasting
TG levels may vary after a recent meal.
Thus, we (Uptodate) generally advise that the lipid profile be measured in the fasting state.
8 to 12 hours without food, early in the morning (before breakfast)
Diagnosis
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Other Test
• FBS
• TSH
• LFT
• Urea , Cr
• Urinalysis
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Indication for Lipid measurement
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k LDLسطح درمان اولیه براساس
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Very HighHigh High
Normal
Normal
≥ 240200-239<200Chol (mg/dl)
≥500Severe
175-499
Moderate
150-174<150TG(mg/dl)
≥190LDL(mg/dl)
HDL(mg/dl)
Serum Lipids Levels
According To patients comorbidity
Low : in M<40 , F<50 cardioprotective : > 60 mg/dl
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2019 ESC/EAC Guidelines for the management of dyslipidemia : lipid modification to reduce cardiovascular risk
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Statin DoseLDL GoalRisk groupDefinition
Risk group
High< 40Very Very
High
High<55Very High
High<70High
moderate<100Moderate
low<116*Low
ASCVD 2th Event during 2 years
ASCVD + other RFDM + TODSevere CKD (GFR <30 cc/min)
ASCVD (ACS , MI, PCI, CABG, Stroke ,TIA ,PAD ,AAA)
DM > 10yr / with other RFModerate CKD (GFR 30-59 cc/min)
LDL ≥ 190 mg/dlRisk 10 yr CAD ≥ 20%
mg/dl
DM <35 yrsDMT2 <50 yrs without other RFRisk 10 yr CAD :10-20%
Risk 10 yr CAD <10%k
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Clinical ASCVD
Is LDL ≥ 190 mg/dl
Age > 75 y
DM?
10-year ASCVD risk score?
Remember ! Secondary cause!
ApproachLDL
Treatment
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Clinical cases Presentation
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Case 1
44 YO woman
C.C:
Increased fatigue, weight gained about 10 kg with no changes in
her life
PMH:
Negative
DH:
Negative
Lab data:
TC: 150 mg/dl TG:112 mg/dl HDL:54 mg/dL LDL:155 mg/dL
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Which is the best recommendation
at this time?
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A. Initiate atorvastatin 10 mg/day
B. Initiate rosuvastatin 20 mg/day
C. Obtain a high-sensitivity C-reactive protein (hs-CRP)
D. Obtain a thyroid panel
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Answer: D
A. Initiate atorvastatin 10 mg/day
B. Initiate rosuvastatin 20 mg/day
C. Obtain a high-sensitivity C-reactive protein (hs-CRP)
D. Obtain a thyroid panel
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Secondary Causes of Lipoprotein Abnormalities
Hypothyroidism
Obstructive liver disease
Nephrotic syndrome
Uncontroled DM
Obesity
Drugs
Unexplained weigh gain
Increased fatigue
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Drug induced DLP
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Drug induced DLP
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Case 268 YO woman
PMH:HTN , hyperlipidemia, presents with an acute MI
DH:metoprolol 50 mg/day, enalapril 20 mg/ day, furosemide 20 mg/day, atorvastatin 20 mg/day, Pantoperazole 40 mg/day, aspirin 80 mg/day, and clopidogrel 75 mg/day.
Lab Data:TC 157 mg/dL, TG 132 mg/dL , HDL 48 mg/dL, LDL 83 mg/dL
She achieved a 35% reduction in her LDL
she has previously not tolerated higher doses of atorvastatin or rosuvastatin because of myalgia.
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Which is the best recommendation at this time to
further reduce her risk of recurrent events?
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A. Add alirocumab 75 mg subcutaneously every 2 weeks
B. Add ezetimibe 10 mg/day
C. Add niacin extended release 500 mg/night
D. Continue atorvastatin 20 mg/day
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Answer: B
A. Add alirocumab 75 mg subcutaneously every 2 weeks
B. Add ezetimibe 10 mg/day
C. Add niacin extended release 500 mg/night
D. Continue atorvastatin 20 mg/day
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Clinical ASCVD
ACS
History of MI
Stable or unstable angina
Coronary or other arterial revascularization
Stroke
TIA
PAD
Aortic aneurysm
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Ezetimibe
• Tab:10mg
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Mechanism of action• Inhibits absorption of cholesterol at the brush border of the small intestine
• This leads to
Decreased delivery of cholesterol to the liver
Reduction of hepatic cholesterol stores
Increased clearance of cholesterol from the blood
Decreased total C, LDL-C, apoB, TG
Increased HDL-C
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Pharmacodynamics and Pharmacokinetics
Onset of action:
– Within 1 week; Maximum effect: 2-4 weeks
Half-life elimination:
– 22 hours
Absorption is not affected by food
Administered at any time of day without regard to meals
No dose adjustment in renal and liver impairment
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ADRDiarrhea
Arthralgia
Cough
Fatigue
Abdominal pain
Back pain
Increased serum transaminases
Ezetimibe should be administered at least 2 h prior or 4 h following
the administration of cholestyramine
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Case 3
43-yo man
CC:
For routine monitoring
PMH:
HTN
FHhypercholesterolemia
Lab data:TC 267 mg/dL, TG 143 mg/dL ,HDL 38 mg/dL, LDL 200 mg/Dl
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Which is the best recommendation for
management?
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A. Initiate cholestyramine
B. Initiate atorvastatin 40 mg/day
C. Initiate ezetimibe 10 mg/day
D. Initiate simvastatin 20 mg/day
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Answer: B
A. Initiate cholestyramine
B. Initiate atorvastatin 40 mg/day
C. Initiate ezetimibe 10 mg/day
D. Initiate simvastatin 20 mg/day
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Statin intensity
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STATIN
Atorvastatin
Tab:10-20-40
Rosuvastatin
Tab:5,10,20
Simvastatin
Tab:10,20
Lovastatin
Tab:20
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Different doses of statins
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Mean additional changes of lipid profile
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Case 4
54 YO man
PMH:DM,HTN, dyslipidemia, GERD
DH:lisinopril 20 mg/day, amlodipine 10 mg/day, atorvastatin 20 mg/day, omeprazole 20 mg/day, metformin 500 BD
Lab data:TC 197 mg/dL, TG 166 mg/dL, , HDL 37 mg/dL,LDL
128 mg/dL. His non-HDL is 160 mg/dL
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which is the best recommendation at this time to
achieve his LDL (and non-HDL) goal?
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A. Add fenofibrate 200 mg/day
B. Change atorvastatin to rosuvastatin 20 mg/day
C. Increase pravastatin to 80 mg/day
D. Add ezetimibe 10 mg/day
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Answer:B
A. Add fenofibrate 200 mg/day
B. Change atorvastatin to rosuvastatin 20 mg/day
C. Increase pravastatin to 80 mg/day
D. Add ezetimibe 10 mg/day
R
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Case 5
A 69 yo woman with CHD, DM, HTN, and GERD is referred to your
lipid clinic because of statin intolerance.
She reports myalgias with rosuvastatin and atorvastatin(40 mg), liver
enzyme elevations with atorvastatin, and GI upset with ezetimibe.
DH:
metformin 1000 mg BD, amlodipine 10 mg/day, lisinopril 10
mg/day, and omeprazole 20 mg/day
Lab data:
TC 238 mg/dL, TG 421 mg/dL, HDL 44 mg/dL, LDL 110 mg/dL,
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Which is the best recommendation at this time to
further reduce her ASCVD risk?
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A. Add cholestyramine
B. Add evolocumab 140 mg SC every 2 weeks
C. Add fenofibrate 200 mg/day
D. Add omega-3 fatty acids 4 g/day
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Answer:B
A. Add cholestyramine
B. Add evolocumab 140 mg SC every 2 weeks
C. Add fenofibrate 200 mg/day
D. Add omega-3 fatty acids 4 g/day
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Evolocumab
PCSK9 InhibitorsSolution for injection:140mg/ml
SC injection
Can be administered bi-weekly or once-monthly
MechanismIncreases the number of ldlrs available to clear LDL from the blood, thereby
lowering LDL-C levels
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Evolocumab
No dosage adjustment necessary in renal and hepatic failure
Most common adverse effect reported are injection site reactions
Evolocumab is FDA-approved for use as monotherapy in
primary hyperlipidemia
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Case 657-year-old woman
CC:
Increased thirst and polyuria
PMH:
HTN , Dyslipidemia, Given a new diagnosis of diabetes , Cigarette smoker
DH:
Enalapril 20 mg/day, Amlodipine 10 mg/day, HCTZ 12.5 mg/ day
Atorvastatin 10 mg/day
Lab Data:
FBS:156 mg/Dl ,HbA1C 7.7%, TC 184 mg/dL, TG 202 mg/dL, HDL 41 mg/dl
LDL 103 mg/dL
SBP:150mmHg
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Which is the best
recommendation at this time?
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A. Add fenofibrate 200 mg/day
B. Add niacin extended release 500 mg/night.
C. Increase atorvastatin to 40 mg/day
D. Continue atorvastatin 10 mg/day
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Answer: C
A. Add fenofibrate 200 mg/day
B. Add niacin extended release 500 mg/night.
C. Increase atorvastatin to 40 mg/day
D. Continue atorvastatin 10 mg/day
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40-75 years and LDL 70-189mg/dl
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10-year ASCVD risk score is 22%
R https://www.mdcalc.com/framingham-risk-score-hard-coronary-heart-disease
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Case 7a 51 yo man
PMH:
DM, HTN, Hypertriglyceridemia, Peptic ulcer disease ,History of acute
pancreatitis
SH:
Drinks 4–6 beers/day
DH:
Enalapril 20 mg/day, HCTZ 50 mg/day, amlodipine 10 mg/day
pantoprazole 40 mg/day, rosuvastatin 20 mg/day
metformin 1000 mg BD, insulin glargine 28 units at bedtime
BMI:38 kg/m2
Lab Data:
HbA1C 6.9%, TC 157 mg/dL, TG 588 mg/dL, HDL 38 mg/dL, LDL 78 mg/dL
LFT:NL Scr:1 mg/dl
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Which best describes potential secondary
causes that may be contributing to his
hypertriglyceridemia?
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A. Alcohol consumption, poorly controlled DM, amlodipine.
B. Alcohol consumption, rosuvastatin, weight loss.
C. Obesity, alcohol consumption, HCTZ
D. Obesity, poorly controlled DM, metformin.
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Answer: C
A. Alcohol consumption, poorly controlled DM, amlodipine.
B. Alcohol consumption, rosuvastatin, weight loss.
C. Obesity, alcohol consumption, HCTZ
D. Obesity, poorly controlled DM, metformin.
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Secondary Causes of HypertriglyceridemiaObesity
Diabetes mellitus
Ileal bypass surgery
Sepsis
Pregnancy
Acute Hepatitis
Drugs:
Alcohol
Estrogens
Isotretinoin
Beta blockers
Glucocorticoids
Bile-acid resins
Thiazides
Azole antifungals
Anabolic steroids
Sirolimus
Alcohol
BMI: 38 kg/m2
Thiazides
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Case 8
A 46-yo woman who was recently (3 months ago) hospitalized for acute pancreatitis (TG greater than 2000 mg/dL) is referred to you for management of hypertriglyceridemia
Since her hospitalization, she has lost 10 kg by reducing her intake of simple carbohydrates and walking for 30 minutes five times a week.
PMH: HTN
DH:
amlodipine 10 mg/day, Atorvastatin 20mg/day , losartan 100 mg/day, multivitamin.
Lab data
TC 210 mg/dL, TG 653 mg/dL, HDL 39 mg/dL ,LDL100mg/dl
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Which is the best treatment recommendation at
this time?
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A. Continue diet, exercise, and weight loss only.
B. Initiate atorvastatin 40 mg/day.
C. Initiate ezetimibe 10 mg/day.
D. Initiate fenofibrate 200 mg/day.
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Answer:D
A. Continue diet, exercise, and weight loss only.
B. Initiate atorvastatin 40 mg/day.
C. Initiate ezetimibe 10 mg/day.
D. Initiate fenofibrate 200 mg/day.
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Fibric Acid Derivatives
GemfibrozilCap:300 mg
Tab:450mg
FenofibrateCap:100-200 mg
Primarily used in patients with TG levels that exceed 500 mg/dl to reduce the risk of acute pancreatitis
Reduce TG 20%-50%
Rise HDL-C 10% to 15%
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Generally well tolerated
Gastrointestinal complaints and transient elevations in transaminaselevels have been reported
Muscle-related adverse effects can occur with both gemfibrozil andfenofibrate alone but is more common when used in combinationwith statins
Gemfibrozil and fenofibrate require dose adjustments for significantrenal impairment
Current guidelines do not recommend gemfibrozil to be initiated inpatients receiving statin therapy
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Case 9
A 34-year-old woman with a history of
heterozygous familial hypercholesterolemia
recently tested positive for pregnancy.
She takes atorvastatin 40 mg/day and ezetimibe
10 mg/day.
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Which is the best recommendation
at this time?
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A. Continue atorvastatin; discontinue ezetimibe
B. Continue ezetimibe; discontinue atorvastatin
C. Discontinue both atorvastatin and ezetimibe; initiate alirocumab 75 mg subcutaneously every 2 weeks.
D. Discontinue both atorvastatin and ezetimibe; initiate cholestyramine twice daily.
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Answer:D
A. Continue atorvastatin; discontinue ezetimibe
B. Continue ezetimibe; discontinue atorvastatin
C. Discontinue both atorvastatin and ezetimibe; initiate alirocumab 75 mg subcutaneously every 2 weeks.
D. Discontinue both atorvastatin and ezetimibe; initiate cholestyramine twice daily.
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Pregnancy
AAP/ACOG guidelines suggest that lipid assessment should
occur annually for all age groups
The NLA suggests women should be screened for
dyslipidemia before pregnancy
Most cholesterol-lowering drugs should be discontinued 1-2
months before getting pregnant or as soon as pregnancy is
discovered
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Pregnancy
The only agents with the historic FDA
pregnancy category B are bile acid
sequestrants and omega-3 fatty acids
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Bile acid sequestrants
Reduce LDL-C (13%-20%)
First line during pregnancy
Not systemically absorbed
Should be avoided in those with TG levels exceeding
300 mg/dl
Poor tolerability profile
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ADR
GI complaints
• Constipation
• Bloating
• Epigastric fullness
• Nausea
• Flatulence
Impaired absorption of fat-soluble vitamins A, D, E, and K
Gastrointestinal obstruction
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Reduced bioavailability of other drugs (warfarin,
levothyroxine, phenytoin)
Drug–drug interactions may be avoided by takingother medications 1 hour before or 4 hours after theBAS
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Omega-3
2-4 g/day of EPA/DHA
Reduce TG and VLDL 20%-50%
Gastrointestinal complaints
Abdominal pain
Caution is advised when used concomitantly with antiplatelet
agents or anticoagulants since omega-3 PUFA may prolong
bleeding time
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Lovaza:
Each 1g cap(EPA:465mg) +(DHA:375mg)
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Case 10
70-yo man
CC:
Bilateral muscle aches in his legs with atorvastatin (40 mg)
PMH:
CAD, HTN
Lab data:
TC 267 mg/dL, TG 143 mg/dL ,HDL 38 mg/dL, LDL 200 mg/dL
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25(OH)D3=28
TFT:NL
LFT:NL
CK:3 ULN
Which one is the best recommendation?
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A. D/C atorvastatin
B. Continue atorvastatin and check CK after few
days
C. Change to atorvastatin 20 mg
D. Change to rosuvastatin
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Answer:B
A. D/C atorvastatin
B. Continue atorvastatin and check CK after few days
C. Change to atorvastatin 20 mg
D. Change to rosuvastatin
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Risk Factor Statin characteristics
Metabolized by CYP 3A4 High dose
Advanced age
Hypothyroidism
Preexisting muscle disease
Renal impairment
Female sex
Diabetes mellitus
lower BMI vitamin D deficiency Chinese (and possibly east asian in general) ancestry
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Muscle symptoms are typicallymuscle weakness,soreness, cramping, stiffness, tendon pain
Bilateral
Symmetrical
Distributed proximally (hip flexor region, upper chest and shoulders)
onset of muscle symptoms is usually within weeks to months
The risk is greatest in the first year of therapy
After a dose increase or the addition of an interacting drug
Symptoms typically improve within 1–2 weeks of statin discontinuation
The risk of rhabdomyolysis is ≈0.01% and is potentially preventable by prompt cessation of statin treatment
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Clinical Aproach to Myopathy or Rhabdomyolysis
Consider other reasons– Unusual or strenuous exercise– Hypothyroidism (muscle weakness and increased CK
levels)
Measure CK– Unexplained muscle symptoms– Unexplained increases above 3 ULN in transaminases
Routine monitoring of serum CK levels is not recommended
Consider drug interaction
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Statin drug interaction
Strong inhibitors 3A4 Moderate inhibitors 3A4 Strong inducers 3A4 Moderate inducers 3A4
Atazanavir Amiodarone Carbamazepine Dexamethasone
Clarithromycin Aprepitant Phenobarbital St. John's wort
Itraconazole Cimetidine Phenytoin
Ketoconazole Cyclosporine Primidone
Lopinavir Diltiazem Rifampin
Voriconazole Erythromycin
Fluconazole
Grapefruit juice
Verapamil
Gemfibrozil
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If CK
>10 ULN (>5 ULN in a vulnerable patient)
statin should be stopped immediately
Start high fluid intake
If the symptom or lab test do not improve soon after statin D/C, should be consider other diagnosis
3 -4 > ULN and mild symptomscontinue statin
check CK in a few days
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Case 11
52-yo man
DH:
Amlodipine , Atorvastatin
PMH:
CAD, HTN
Lab data:
TC 267 mg/dL, TG 143 mg/dL ,HDL 38 mg/dL, LDL 100 mg/dL
ALT:120 AST:80 ALP:150
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Which one is the best recommendation?
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A.Hold atorvastatinand check LFT after 3 days
B.Continue atorvastatin and check LFT after 3 days
C.Chane to atorvastatin 20 mg
D.Change to rosuvastatin
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Answer:A
A. Hold atorvastatinand check LFT after 3 days
B. Continue atorvastatin and check LFT after 3 days
C. Change to atorvastatin 20 mg
D. Change to rosuvastatin
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If ALT or AST is 1 to 3 times the ULN No need to discontinue the statin
If ALT or AST exceeds 3 times the ULNHold statin
Repeat LFT
If a patient’s transaminase levels continue to rise
Or If there is further objective of liver injuryThe statin should be discontinued
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LOW HDL
LOW HDL: component of Metabolic syndrome , associated with high TG ,High LDL
Most common form of dyslipidemia in Iran
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LOW HDL treatment Life style Modification :
Obesity , Physical activity , stope Smoking , stress
carbohydrate , fruits & Vegetable
Pharmacotherapy:
IF low HDL + High LDL : statin
IF low HDL + High TG : statin or fibrate (According to TG level)
IF isolated Low HDL : no recommendation for drug treatment
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