Pharmacotherapy management of dyslipidemia

1. Dyslipidemia
Dr Bedeer Elsherbiny
PharmD BCPS BCMTM

2. Objectives
Pharmacologic treatment for dyslipidemia
Medications used for dyslipidemia
Nonpharmacologic recommendations
Practice questions

3. Pharmacologic recommendations:
Secondary ASCVD
prevention
Severe
hypercholesterolemia
(LDL-C ≥190 mg/dL)
Diabetes mellitus
(DM)
Primary prevention of
ASCVD
ASCVD: stroke MI
High intensity statin Moderate intensity statin

4. Total Cholesterol
<200 mg/dL (<5.17 mmol/L) Desirable
200-239 mg/dL (5.17-6.20 mmol/L) Borderline high
≥240 mg/dL (≥6.21 mmol/L) High
LDL Cholesterol
<100 mg/dL (<2.59 mmol/L) Optimal
100-129 mg/dL (2.59-3.5 mmol/L) Near or above optimal
130-159 mg/dL (3.36-4.13 mmol/L) Borderline high
160-189 mg/dL (4.14-4.90 mmol/L) High
≥190 mg/dL (≥4.91 mmol/L) Very high
HDL Cholesterol
<40 mg/dL (<1.03 mmol/L) Low
≥60 mg/dL (≥1.55 mmol/L) High
Triglycerides
<150 mg/dL (<1.70 mmol/L) Normal
150-199 mg/dL (1.70-2.25 mmol/L) Borderline high
200-499 mg/dL (2.26-5.64 mmol/L) High
≥500 mg/dL (≥5.65 mmol/L) Very high
Lab values for lipid panel
fasting for 8 to 12 hours

5. Common Secondary Causes of Elevated LDL-C and TG
Increase LDL-C
• Amiodarone
• cyclosporine
• diuretics
• Glucocorticoids
Increase TG
• Anabolic steroids
• atypical antipsychotics
• β-blockers
• bile acid sequestrants
• glucocorticoids
• protease inhibitors
• raloxifine
• retinoic acid
• sirolimus
• tamoxifen
• thiazides
Medications

6. Common Secondary Causes of Elevated LDL-C and TG
Increase LDL-C
• Saturated or trans fats
• weight gain
• anorexia
Increase TG
• Very low-fat diets
• high carbohydrate intake (refined)
• excess alcohol
• weight gain
Dietary Factors

7. Common Secondary Causes of Elevated LDL-C and TG
Increase LDL-C
• Nephrotic syndrome
• biliary obstruction
• hypothyroidism
• obesity
• pregnancy
Increase TG
• hypothyroidism
• obesity
• pregnancy
• nephrotic syndrome
• Poorly controlled diabetes
• chronic renal failure
Disease states

8. ACC/AHA Guidelines

9. Pharmacologic management of dyslipidemia
initiate statin therapy, Optimize statin therapy
(high intensity or maximally tolerated dose)
add ezetimibe if indicated
consider PCSK9-inhibitors (PCSK9-I)

10. • Inhibits enzyme responsible for converting HMG-CoA to mevalonate
(rate limiting step in production of cholesterol)
Mechanism of
action:
• Myopathy
• check creatine kinase [CK] at baseline and then only if muscle symptoms occur
• no regular monitoring
• Elevated liver enzymes
• Obtain LFTs at baseline in all patients
• Perform repeated LFTs only when clinically indicated.
• Monitor for symptoms of hepatic injury.
Adverse effects and
monitoring
• Active liver disease, unexplained persistent elevations in hepatic transaminases
• Certain medications
• Pregnancy and breastfeeding
Contraindications
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins)

11. • Increased risk of myopathy and rhabdomyolysis when coadministered with
statins.
• Risk is greater with gemfibrozil than with fenofibrate.
Fibrates
• Doses greater than 1 g/day increase the risk of myopathy and rhabdomyolysis
when used concomitantly with statins;
• risk is lower than with fibrates;
• statins and niacin are commonly used together; monitor for muscle pain.
Niacin
• A case report of a myopathy attributed to a drug interaction between
canagliflozin and rosuvastatin was recently reported.
Canagliflozin
Drug Interactions

12. Statin Intensity

13. Mechanism of action:
• Inhibition of cholesterol
absorption
Adverse effects and
monitoring:
• Diarrhea,
• upper respiratory tract
symptoms;
• no monitoring necessary
Data suggest that
• combination with
simvastatin is superior to
simvastatin alone in
prevention of CV events.
Ezetimibe

14. PCSK9 Inhibitors Evolocumab
Alirocumab
Efficacy:
• Lower LDL-C by an
additional 45%–68%
when combined with
statin therapy;
• reduce CV events when
added to statin therapy
Mechanism of action:
• Monoclonal antibodies
that inhibit a protein
called PCSK9,
increasing cholesterol
clearance from the liver
Indications
Both:
• heterozygous familial
hypercholesterolemia
• clinical ASCVD
Evolocumab:
homozygous familial
hypercholesterolemia
(HoFH)

15. Familial hypercholesterolemia(FH)
This term is used for individuals that meet the following three criteria:
• High TC, TG usually normal
• Deposition of LDL-derived cholesterol in tendons and arteries (xanthomas, atheromas)
• Hypercholesterolemia caused by an inherited autosomal trait
• Treatment of dyslipidemia to prevent or delay the onset of atherosclerotic
cardiovascular disease (ASCVD).
Primary prevention
• Treatment of dyslipidemia to prevent progression of ASCVD or recurrent ASCVD
events.
Secondary prevention

16. PCSK9 Inhibitors Dosage
Evolocumab
o Heterozygous familial hypercholesterolemia
or clinical ASCVD:
140 mg SC every 2 weeks or
420 mg SC once monthly
o Homozygous familial hypercholesterolemia:
420 mg SC once monthly
Alirocumab
• Initial dose,
5 mg SC every 2 weeks or
300 mg subcutaneously every 4 weeks;
• if LDL-C reduction inadequate,
adjust dose to 150 mg SC every 2 weeks

17. Bile acid sequestrants
cholestyramine colestipol colesevelam
• Bind to bile acids to disrupt enterohepatic recirculation of bile acids.
Liver is stimulated to convert hepatocellular cholesterol to bile acids.
Mechanism of action:
• GI distress
• constipation
Adverse effects:
• Decreased absorption of many drugs including:
warfarin, amiodarone, levothyroxine, ezetimibe, digoxin, and thiazides;
• administer drugs 1–2 hours before or 4 hours after bile acid sequestrant
Drug Interactions
• Complete biliary obstruction,
• raised TG concentrations (especially greater than 400 mg/dL)
Contraindications:

18. Niacin
Mechanism of action:
• Inhibits mobilization of free fatty acids from peripheral adipose tissue to the liver
and reduces synthesis of TG, very-low-density lipoproteins, and LDL-C
Adverse effects and monitoring:
• Flushing,
• hyperglycemia,
• hyperuricemia,
• myopathy,
• upper GI distress,
• increased hepatic transaminases;
• monitor LFTs at baseline, every 6–12 weeks for first year and then yearly
• Sustained release is more hepatotoxic than extended-release or immediate-release preparations.
• Extended-release niacin is less likely to cause flushing.
Contraindications: liver disease and active peptic ulcer disease.
Caution in patients predisposed to gout
Flushing can be minimized by
• aspirin or an NSAID 30–60 minutes before niacin,
• taking at bedtime with food,
• slow titration
• avoiding hot beverages, spicy foods, and hot showers around the time of administration.
According to the 2018 AHA/ACC cholesterol guidelines,
• no clear indications for routine niacin use for reduction of LDL-C.

19. Fibrates
Mechanism of action:
• Reduces rate of
lipogenesis in the
liver
Adverse effects and
monitoring:
• Dyspepsia
• gallstones
• myopathy
• increased hepatic
transaminases.
• Monitor LFTs every 3
months during first
year and then
periodically.
Contraindications:
• Severe renal or
hepatic disease
• pre-existing
gallbladder disease
Indication:
• treatment of severe
hypertriglyceridemia
(TGs 500 mg/dL or
greater
Fenofibrate

20. Omega-3 fatty acids
Mechanism
of action:
• Reduction of hepatic production of very-low-density lipoproteins;
• possible reduction in hepatic synthesis of TG; increased hepatic β-oxidation
Adverse
effects:
• Arthralgia,
• GI effects (e.g., burping, taste perversion, dyspepsia); at more than 3 g/day,
• bleeding (because of inhibition of platelet aggregation)
Dose:
• 2–4.8 g/day as a single dose or in two divided doses

21. Patients age >75 years
initiate a moderate-
intensity statin or continue
a moderate- or high-
intensity statin if :
benefits outweigh risks
Discontinue statin
therapy if patients have:
functional decline
multimorbidity
frailty
reduced life expectancy
Hypertriglyceridemia
Primary goal is to prevent
pancreatitis
Evaluate for secondary
causes
Moderate
hypertriglyceridemia
( TG 175-499 mg/dL)
Treat lifestyle factors,
comorbidities, and
medications which
increase TGs
If persistently elevated
and ASCVD risk ≥7.5%,
consider initiation or
intensification of statin
therapy
Severe hypertriglyceridemia
(TG ≥ 500 mg/dL)
If persistently elevated and
ASCVD risk ≥7.5%,
consider initiation or intensification of
statin therapy
implement a very low-fat diet and
initiate
fibrate or omega-3 fatty acid
to prevent acute pancreatitis,
if fasting TG ≥ 1000 mg/dL
Patients age >75 years
Special Populations

22. Heart-healthy diet
• Dietary Approaches to Stop Hypertension (DASH) diet or the Mediterranean Diet
• Fruits, vegetables
• whole grains
• low-fat dairy products
• skinless poultry
• and fish
• nuts and legumes
• Limit sweets, sugar-sweetened beverages and red meats
• Lower intake of saturated fats and replace with unsaturated fats
(especially polyunsaturated fats)
Regular exercise
• Engage in moderate-to-vigorous intensity aerobic physical activity
3-4 times per week for an average of 40 minutes per session
Smoking cessation
Nonpharmacologic recommendations

23. According to the ACC/AHA blood cholesterol
guidelines, which is best described as a high-intensity
statin dose?
A. Pravastatin 20 mg/day.
B. Lovastatin 20 mg/day.
C. Atorvastatin 40 mg/day.
D. Rosuvastatin 10 mg/day.
Practice Questions

24. Which best describes a potential
secondary cause of high TG
concentrations?
A. Amiodarone.
B. Biliary obstruction.
C. Sirolimus.
D. Saturated fats.
Practice Questions