6. DYSLIPIDEMIA
• Dyslipidemias are
generally characterized
clinically by increased
plasma levels of
cholesterol, TGs, or both,
variably accompanied by
reduced levels of HDL
cholesterol
Dyslipidemia
Familial/Genetic
Secondary
13. Non
Pharmacological
Management
• Clinical studies – 30% to 40% reduction of
serum cholesterol, LDL, and TGs with the
combination of diet, lifestyle modifications,
and nutritional supplements in most
patients.
17. STATINS
• HMG-CoA reductase*
• On LDL: dose dependent reduction till 50%
• On TG: 10 to 20% reduction from baseline
• ADVERSE EFFECTS
1. Muscle – myopathy> rhabdomyolysis
2. Liver- ALT raise> liver failure
3. New onset Diabetes
HMG-CoA
reductase
inhibition
reduction in
intracellular
cholesterol
increased
LDL
receptor
increased
uptake of
LDL
18. • Metabolism through the CYP system except pravastatin, rosuvastatin,
and pitavastatin
• gemfibrozil enhances the risk of myopathy
19. • Before starting check TSH, HbA1c, SGPT, Urine Proteins, S.Creatinine,
total CPK
• Titrate dose of statins according to LDL
• Avoid Alcohol
• Check CpkMB If complains muscle pain
• short-acting statins - in the evening – Simva, Lova, Prava
• Long-acting statins – at any time of the day – Atorva, Rosuva,
Pitava
21. Cholesterol absorption inhibitors
inhibiting cholesterol
absorption at intestine
upregulating LDLR
expression
increased clearance of
LDL
Ezetimibe- monotherapy at 10 mg/day reduces LDL-C by 15 to 22%
- with statin additional 21 to 27%
Adverse Effects: diarrhea, respiratory infections, fatigue
22. Bile acid sequestrants
Blocks EHC
Need to increase more
cholesterol synthesis
More LDL receptors
• Reduction in LDL-C of 18 to 25%
• 24 g of cholestyramine OD
• 20 g of colestipol OD
• 4.5 g of colesevelam OD – best of class
• To be taken 4hr before or 1 hr after other drugs
• Adverse effects
1. GI -------- low dose, ample fluid
2. Increase TG
23. PCSK9 inhibitors
Mabs against PCSK9 –
1. Alirocumab 75mg s/c once 2 weekly
2. Evolocumab 140 mg s/c once 2
weekly
• Reduce LDL by 46 to 73%
• Reduce TG by 26% in phase2 trials
• Reduce Lp(a) 30 to 40% in phase 2
Adverse Effects
1. Local
2. Flu like symptoms
3. Immunological
24. Microsomal TG transfer protein inhibitor
• Lomitapide – oral daily 5mg to max 60 mg
- taken 2hrs before meals
• Reduction of LDL by 50%
• Used in HoFH studies
• Cyp3A4 metabolism so Interactions
• Adverse effects- GI side effects 🩺 limiting
- Fatty liver, raised enzymes
25. Mipomersen
• Antisense Oligonucleotide to mRNA of ApoB100
• 200 mg weekly s/c injection
• Metabolised by tissue endo and exo nucleases
• Used mostly in HoFH
• Adverse Effects
1. Local
2. Steato-hepatitis – 3 monthly LFT monitoring
3. Flu like symptoms
Hybridization
in liver
Degradation
by RNAse H
Low ApoB100
27. • Drugs –
1. Gemfibrozil 600mg tab bid
2. Fenofibrate 40mg, 120mg once daily tab
• Effects
1. 50% reduction in TG
2. <20% reduction in LDL
3. <20% increase in HDL
• Increased risk of myopathy if prescribed along with statins- less with
Fenofibrate
• Adverse Effects- GI, skin rash, pancreatitis, Cholelithiasis
• Monitor : S.Creatinine, SGPT, CK-MB if prescribed along with statins
28. Newer Drugs
• CETP Inhibitors - Anacetrapib –
1. raises HDL-C and ApoA-I levels (by 104 and 36%, respectively)
2. lowers LDL-C and ApoB (by 17 and 18%, respectively)
• Only Anacetrapib has shown reduced coronary events by 9%
• Apolipoprotein A1 mimetic – D-4Fpeptide - reverse cholesterol
uptake
• Thromimetic – Sobetirome, Eprotirome
29. Bempedoic acid inhibits cholesterol synthesis by inhibiting the action of ATP citrate lyase
Small interfering RNA (siRNA) molecule Inclisiran— inhibits the synthesis of PCSK9—reduced
LDL-C by up to 50%
Evinacumab is monoclonal antibody that is an inhibitor of angiopoietin-like 3 which
regulates lipid metabolism by increasing triglycerides
Volanesorsen is an antisense oligonucleotide - binds to apoC-III mRNA - leading to its
degradation and preventing translation of apoC-III protein, which inhibits triglyceride
metabolism and hepatic clearance of chylomicrons
30. Miscellaneous Phytosterols 1.6 to 3.0 g/d in divided doses with food
Red yeast rice 2400 mg per night
Pantethine: 300 mg 3 times per day
Niacin various forms at 500 to 3000 mg/d
Soy
γ-/δ-Tocotrienols: 200 mg per night with food
ω-3 Fatty Acids: at 3 to 5 g/d at a ratio of 3 parts
EPA, 2 parts DHA, and GLA
32. What are we
trying to do
with these
drugs?
ASCVD
Major ASCVD events includes
1. Recent ACS (within the past 12 mo)
2. History of MI (other than recent ACS
event listed above)
3. History of ischemic stroke
4. Symptomatic peripheral arterial
disease
33. High-Risk Conditions include
1. Age ≥65 y
2. Heterozygous familial hypercholesterolemia
3. History of prior CABG or PCI outside of the major ASCVD event(s)
4. Diabetes mellitus
5. Hypertension
6. CKD (eGFR 15-59 mL/min/1.73 m2)
7. Current smoking
8. Persistently elevated LDL-C (LDL-C ≥100 mg/dL
9. History of congestive HF
Very High-Risk Conditions include
1. Multiple major events
2. 1 Major plus multiple high risk conditions
36. • High dose statin therapy is initiated or continued as
early as possible
• Goal 50% reduction of LDL-C, to <55 mg/dL
• Initial Ezetimibe then PCSK9 inhibitors
• Loading with high dose statins before PCI.
• Intensive statin therapy after TIA & Stroke
41. DIABETES
• IA--- > 40 to 75 years age with diabetes– moderate intensity Statins
• II A---- assess ascvd risk and If multiple RFs – higher intensity Statins
to reduce ldl by 50 %
• II A ---- > 75 years-old, if on statins- continue
• II B --- Adults with diabetes with ascvd risk >20% -add ezetimibe.
• II B----- >75 years old with DM, not on statins – start based on risk-
benefit ratio
42. Old age
• For given TC higher risk in elderly.
• Multiple co-morbities, Medications
• Different pharmacokinetics and dynamics
• Statins to be started at low doses and titrate.
43. Children
• Family history of early CVD & hypercholesterolemia – screening from
2years
• With obesity and Metabolic syndrome- testing
• Lifestyle changes and caloric restrictions.
• >190 or >160 mg/dL with FH after failure of above
• Reverse cascade of screening.
44. WOMEN
• Statins are preferred.
• OCPs ? >160mg/dL
• Oestrogen Replacing therapy ?
• Pregnancy and lactation BAS and lipid apheresis
45. CKD
• Increased risk of both
atherosclerotic vascular
disease and structural
heart disease
• Specifically rise of TG,
Lp(a)
47. Inflammatory conditions
• Rheumatoid arthritis (RA), glomerulosclerosis, or pulmonary fibrosis
• CVD has been cited as the top cause of death in people with
RA
• HIV - Immune dysregulation, Systemic inflammation, Antiretroviral
therapy & Dyslipidemia
• Role of hs-CRP, CAC, intimal thickness.
• Assess Risk score and start based on score
• Start on low doses and check for drug interactions.
48. Raised TG
• TGs are associated but not causal for ascvd
• Drugs used are statins, fibrates, niacin, ω-3 Fatty Acids
• Treatment to be started If > 200 mg/dL
• Lifestyle and dietary modifications
• 885 and 1000
• Lipid apheresis, And insulin infusion till 500
51. Lipoprotein (a)
• Screen if Premature ASCVD, Familial
• Limited evidence in reducing ascvd on lowering levels
• Drugs – PCSK9 inhibitors, Niacin
• Statins increase
52. References
• 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid
modification to reduce cardiovascular risk
• 2018AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA
/PCNA Guideline on the Management of Blood Cholesterol
• Braunwald's Heart Disease: A Textbook of Cardiovascular
Medicine, Eleventh Edition
• KDIGO Clinical Practice Guideline for Lipid Management in
Chronic Kidney Disease
• Upt0date
