This document provides information on the management of dyslipidemia. It discusses non-pharmacological treatment including lifestyle changes like exercise and diet. Pharmacological treatments for dyslipidemia are also outlined, including statins, fibrates, bile acid resins, nicotinic acid derivatives, cholesterol absorption inhibitors, and fish oil supplements. The mechanisms of action, dosages, adverse effects and patient counseling points are described for each drug class.

1. MANAGEMENT OF
DYSLIPIDAEMIA
By
VISHWANATH GOUDA
1st M.Pharm (Pharmacy Practice)
NGSMIPS, Mangaluru.

2. • Hyperlipidaemia/Dyslipidaemia is an abnormal
amount of lipids (cholesterol or fat) in the blood.
 It is a disorder of lipoprotein metabolism,
including lipoprotein overproduction or
deficiency.
 In developed countries, most dyslipidemias are
hyperlipidemias that is an elevation of lipids in
the blood often due to diet and lifestyle.
2

3. TREATMENT
NON-PHARMACOLOGICAL
1. LIPID PROFILE
 A random serum TC and HDL level, a complete profile of triglycerides is
checked, before commencing the treatment.
 Serum concentrations should not be done after a meal, and hence, the patients
are made to fast for 12-15 hrs before they are measured.
 Patients are made to sit for 5 min prior to withdrawing of blood sample.
 The LDL levels are calculated using Friedewald equation:
LDL = LDL-C (Total cholesterol HDL-C) - (0.45 triglyceride) mmol/L.

4. 2 LIFESTYLE
 Prior to lipid lowering certain lifestyle should be changed like
 smoking,
 alcohol intake,
 obesity,
3 EXERCISE
 Moderate amounts of aerobic exercise (brisk walking, jogging,
swimming, cycling) on a regular basis have effect on lipid
profile.
 Middle aged men exercising for 30min , 3 times a week, have
shown effect within 2 months.

5.  For individuals who are not routinely active exercise of
moderate-intensity on atleast 5 days/week for 30min is
effective.
 For active individuals, vigorous aerobic exercises for 20-
30min 3times/week is recommended.
 In case of secondary prevention , delayed treatment is not
appropriate.

6.  BODY WEIGHT AND WAIST MEASUREMENT:-
 Based on BMI( kg/m²), a individual is classified as
• BMI 18.5 : underweight
• BMI 18.6-24.9 : ideal
• BMI 25-29.9 : overweight (low health risk)
• BMI 30-40 : obese (moderate health risk)
• BMI >40 : morbidity obese ( high health risk).
 Target waist circumference should be <102 cm in white Caucasian
men,<88 cm in white Caucasian females and in Asians <90 cm in
men and <80 cm in females.

7. DIET CONTENTS AND USE dose/day
1) FISH(fish oil supplements) Omega -3 fatty acids , reduces the
level of triglycerides in the body
20g/day
2) TRANSFAT Intake should be reduced to less
than 0.5% , generally present in
bakery prdts, deep fried items.
>0.5%
3) STANOL ESTERS AND PLANT
STEROLS
Reduces the cholesterol
absorption from GIT and reduce
LDL level by 6-15%
2-3g/day
4) ANTIOXIDANTS Most imp as they reduce oxidized
LDL levels
5) SALT Produce adv. Effects on BP and
CHD
Reduced from
150mmole(9g
)-
100mmole(6g
)

8. PREVENTION
SECONDARY
PREVENTION
-LIPID LOWERING
AGENTS TO LOWER
TC<4mmole/L
AND LDL-C < 2mmole/L
-INFORMATION ON
MODIFIABLE RISK
FACTORS PHYSICAL
ACTIVITY, ALC INTAKE,
WEIGHT AND DIABETES
-
-LOW DOSE
ASPIRIN75mgdaily)
-ACE INHIBITORS IN
PATIENTS WITH
HYPERTENSION,
DIABETES
-B-BLOCKERS WITH
THOSE WITH MI
AND HEART FAILURE
- WARFARIN OR
ASPIRIN IN THOSE
WITHATRIAL
FIBRILLATION AND
STROKE
PRIMARY PREVENTION
-LIPID LOWERING
AGENT LIKE
SIMVASTATIN
(40mg/day)
-INFORMATIO ON
MODIFIABLE RISK
FACTORS LIKE
PHYSICAL FITNESS,
ALCOHOL INTAKE ,
SMOKING CESSATION
-ADVICE AND
TREATMENT TO
ACHIEVE BP BELOW
140/90 mmHg
-ADVICE AND
TREATMENT TO
ACHIEVE BP AT LEAST
BELOW 140 /90
MMHG.
-TIGHT CONTROL OF
BP AND GLUCOSE IN
THOSE WITH
DIABETES

9. LIPID LOWERING THERAPY
 Statins
 Fibrates
 Bile acid binding agents
 Cholesterol absorption inhibitors
 Nicotinic acid and derivatives.
9

10. PHARMACOLOGICAL THERAPY
CATEGORY MECHANISM OF ACTION
BILE ACID RESINS CHOLESTYRAMINE The primary action of BARs is to bind bile acids in the
intestinal lumen, with a concurrent interruption of
enterohepatic circulation of bile acids, which decreases
the bile acid pool size and stimulates hepatic synthesis of
bile acids from cholesterol. Depletion of the hepatic pool
of cholesterol.The liver then produces more bile acid to
replace those that have been lost becoz the body uses
cholesterol to make bile acid this reduces LDL level in the
blood.
CHOLESTIPOL
COLESEVELAM
NICOTINIC ACID
AND DERIVATIVES
NIACIN It reduces hepatic synthesis of VLDL, which in turn leads to
reduction in the synthesis of LDL
STATINS(HMG CO-
A REDUCTASE
INHIBITORS)
ATORVASTATIN
ROSUVASTATIN
Statin inhibits HMG CO-A reductase, interrupting
conversion of HMG CO-A to mevalonate, the rate limiting
step in the biosynthesis of cholesterol.
FLUVASTATIN
SIMVASTATIN
LOVASTATIN

11. CATEGORY MECHANISM OF ACTION
FIBRIC ACIDS GEMFIBROZIL It reduces the synthesis of VLDL, to
lesser extent apo protein B with
concurrent removal of triglyceride rich
lipoproteins from plasma
FENOFIBRATE
CLOFIBRATE
CHOLESTEROL
ABSORPTION INHIBITORS
EZETIMIBE Prevents absorption of cholesterol
from brush border of intestine and
blocks cholesterol reabsorption from
GIT
FISH OIL SUPPLEMENTS LOVAZA It reduces TC, VLDL, LDL-C and elevates
HDL-C

12. STATINS
 These are primary and secondary choice of drugs in prevention of
CVD
 The efficacy of statins has been demonstrated in a number of
landmark, randomized placebo-controlled trials.
 SIMVASTATIN(40mg) has poor patient adherence as 50%
withdraw within 12 months and 75% within 3 yrs.
 ROSUVASTATIN is the most potent and is reserved as second line
for patients with inadequate response to first line statins.
 CERIVASTATIN was removed from market

13. • The statins bind to and inhibit the enzyme HMG-CoA
reductase, the rate-limiting step in cholesterol
biosynthesis.
• The inhibition of HMG-CoA reductase activity results
in a drop in intracellular cholesterol production, thus
activating primarily hepatic LDL receptors and
increasing the clearance of LDL from the bloodstream.
• Reduction in total cholesterol, LDL, VLDL,
triglycerides with increase in HDL.
13

15. ADVERSE EFFECTS
o Gastro-intestinal symptoms
o Muscle aches
Less common are,
o Hepatitis
o Rashes
o Headache
o Insomnia
o Nightmares
o Difficulty concentrating
o Myopathy

16. CONTRAINDICATON
• Statins have the potential for serious adverse
reactions in nursing infants.
• Women who require treatment should not
breastfeed their child.

17. BILE ACID RESINS:
DRUG DOSES
COLESTYRAMINE 4g sachet twice a day.
Over 3-4 weeks the dose is built up 12-24g daily taken in
water or suitable liquid.
Occasionally 36g a day is required.
COLESTIPOL Available in granular form. 5g once or twice daily taken in
an appropriate liq.
Dose is increased every 1-2 months to max 30g dose in
single or divided dosage regimen
COLESEVALAM 6 times more potent as it binds to glycocholic acid.
Administered as 625mg tablet to a maximum 4.375g/day (
7 tabs).
Taken as single or twice daily regimen

18. • Bile acid resins exchange an anion, usually sodium, for bile
acids in the intestinal tract.
• This interrupts the recycling of bile acid through enterohepatic
circulation, causing hepatic cells to be stimulated to convert
more cholesterol into bile acids.
• This process up regulates the LDL receptors and enhances
LDL clearance from the plasma.
• Therefore, bile acids resins exert their primary effect on LDL
cholesterol.
18

19. ADVERSE EFFECTS
o Constipation
o Heartburn
o Bloating
o Flatulence

20. PATIENT COUNSELLING
 Palatability is the major problem of BAR’s and patients should
be motivated with the problems they may encounter
 All patients receiving a bile acid binding agent should be
advised that reduced absorption with co-administered drugs
should be anticipated.
 Medication that has to be taken should be administered 1 h
before (at least 4 h for colesevelam) or atleast 4 h after the bile
acid binding agent. As a consequence, for individuals on
multiple drug therapy, bile acid binding agents may not be
appropriate for this reason alone

21. NICOTINIC ACID DERIVATIVES
Nicotinic acid derivatives (NIACIN) has
pharmacological doses of 1.5-6g
Can be used a combination with statin or by itself for
patients with statin intolerance or stain inappropriate.

22. NIACIN
• Niacin is a water-soluble vitamin B that exerts its lipid-lowering
effect by inhibiting the production of VLDL particles in the liver.
• This results in a decrease in triglycerides and LDL.
• Niacin may also increase HDL levels by reducing its catabolism.
• Niacin is an ideal agent for patients who have elevated LDL and
triglyceride levels and a normal or low HDL level
• Nicotinic acid tablet 50mg

23. ADVERSE EFFECTS
 Flushing in head, neck, upper torso-major reason of
discontinuation of drug – major side effects
 Less common are
o Postural hypertension
o Diarrhea
o Exacerbation of peptic ulcers
o Hepatic dysfunction
o Gout
o Increased blood glucose levels

24. FIBRATES
 In addition to its effect on lipoproteins, it has additional
advantages like
 fibrinolytic and clotting mechanisms
 Improvement in glucose tolerance
 FENOFIBRATE produces sustained uricosuric effect on chronic
administration in patients with elevated triglycerides and gout
 FIELD INVESTIGATORS study revealed the safety of
fenofibrate in type-2 diabetes
 Fibrates can be used as first line in patients with hyper
triglyceridemia

25. • Fibrates principally lower triglycerides by increasing the
activity of lipoprotein lipase, the enzyme involved in
hydrolysis of triglycerides from VLDL and LDL
particles.
• This effect is mediated through stimulation of
peroxisome proliferator-activated receptors (PPAR).
• Fibrates may also decrease the formation of VLDL and
thereby have modest effects on lowering LDL
cholesterol.
• Fibric acid derivatives generally provide a triglyceride
reduction of 20% to 30%, decrease LDL by up to 20%,
and increase HDL by 10% to 20%. 25

27. ADVERSE EFFECTS
 Muscle pain
 Unusual tiredness
 Weakness
 Myopathy

28. CHOLESTEROLABSORPTION INHIBITORS
 EZETIMIBE is a 2- azetidinone derivative
 It reduces LDL –C by 15-20% when added to diet
 Brings about a small increase in HDL-C and a reduction in triglycerides
 When added to statin, ezetimibe lowers LDL-C more than with a statin
alone.
 Generally prescribed with a statin, fibrates or nicotinic acid derivatives or
alone and in statin in tolerated individual's

30. FISH OIL SUPPLEMENTS
 FISH OIL preparation are rich in omega -3 fatty acids
 Several studies suggest that this oil protects against CHD events
mortality, sudden death, rather than lipid lowering efficacy
 Commercially available products are
i. Containing omega-3 acid ethyl esters
ii. containing omega -3 –marine triglycerides

31. SOLUBLE FIBRE
 ISPAGHULA HUSK preparations contains soluble fibres reduces
lipid levels.
 These fibres bind to bile acids in the gut and increase conversion of
cholesterol to bile acids in the liver.
 They are less effective than statins in reducing TC and LDL-C.

32. CHOLESTEROL ESTER TRANSFER
PROTEIN (CETP) INHIBITORS
 Low levels of CETP are associated with increased
levels of HDL-C and reduced cardiovascular risk
 CETP transfers cholesterol from HDL-C to LDL-C and
VLDL-C, thereby altering the HDL-C: LDL-C ratio
 Inhibitors of CETP produce a beneficial cardiovascular
effect.

33. COMBINATION DRUG THERAPY
 Generally considered after adequate trials of
monotherapy and for patients documented to be adherent
to prescribed regimen.
 2-3 lipoprotein profiles at 6 week interval should confirm
lack of response prior to combination therapy.
 Statin+ BAR or niacin + BAR provides greatest reduction
in TC

34.  week interval should confirm lack of LDL-C
 Regimen intended to increase HDL include either
GEMFIBROZIL or NIACIN
 Statin combined with either gemfibrozil or niacin causes
hepatotoxicity or myositis.
 Familial combined hyperlipidemia may respond better to
a fibrate +statin than fibrate+ BAR.

36. TREATMENT OF DIABETIC DYSLIPIDEMIA
 Characterized by hypertriglyceridemia, low HDL , and minimally
elevated LDL.
The primary target is to lower the LDL to <100mg/dL
 When LDL > 130mg/dL then patients require simultaneous
lifestyle modification and drug therapy
 Drug therapy for atherogenic dyslipidemia is fibrates and niacin
 Statins are considered to be drug of choice as LDL is target.

37. NEWER DRUGS
Regeneron pharmaceuticals& sanofi issued results of phaseIII
trial of praluent(alirocumab) involving high risk patients with
hypercholesterolemia.
Alirocumab is a monoclonal antibody labelled for the treatment
of hyperlipidemia in patients with heterozygous familial
hypercholesterolemia or clinical atherosclerotic cardiovascular
DRUG DOSAGE DOSE FORM
Alirocumab(praluent) 75mg via sc inj every two
weeks increasing to
150mg every two weeks
Prefilled75mg or 150mg
syringe/pen

38. ADR
• Nasopharyngitis
• Injection
reactions(swelling,pain,itching,redness,tenderness)
• Influenza
• Urinary tract infection
• Diarrhoea
• Bronchitis
• Muscle pain
• Cough

39. EVOLUCUMAB
• Evolucumab further reduces LDL cholesterol by
about 66 to 75% when added to statin.
• Evolucumab reducesLDL more than Ezetimibe .
• Evolucumab added to statins such as
Atorvastatin,Rosuvastatin,simvastatin
• It is a monoclonal antibody that binds to
pcsk9(proprotein convertase subtilisin kexin type 9)
LDL is cleared from the circulation preferentially
through the LDL receptor pathway

40. Pcsk9 is a serine protease that destroys LDLR(receptor)
in the liver,resulting in decreasedLDL-C clearance
&increased plasma LDL-pcsk9 inhibitors decrease
LDLR degradation by pcsk9& therby improve LDL-C
decrease&lower plasma LDL-C
DRUG DOSE
DOSAGE
FORM
Evolucumab 140mg/ml in single
use
420mg/3.5ml in
single use
Single use
prefilledautoinjecto
r
On body infusor
With prefilled
catridge

41. ADR
• Nasopharyngitis
• Respiratory tract infection, influenza
• Injection site reactions
• UTI, sinusitis, headache, myalgia, Dizziness,
• Hypertension, gastroenteritis,
• Arthralgia, nausea, fatigue, musclespasm

42. 4S (Scandinavian Simvastatin
Survival Study) Trial
• It is a secondary intervention trial in large number of patients.
• Simvastatin, 20 to 40mg/day, reduced LDL cholestrol by 35%
and reduced risk of death from any cause by 30%.
• Coronary death are also reduced with simvastatin.
• Therapy was also shown to be effective in women(18%-
19%patients enrolled) and in elderly≥60years

43. The relative risk of death or major coronary event was
reduced to a greater event in elderly than in younger
patients.
Death from non cardiovascular causes was similar for
simvastatin and Placebo.
The 4s study clearly demonstrates the benefit in cholesterol
lowering and long held fears of death from non CHD
causes.

44.  T.H Eric, R.G Drick, L.H Linda. Clinical Pharmacy and
Therapeutics 4th edition. USA. Williams and Wilkins
publication 2011. chapter 9 Hyperlipidemia, P:199-205
T.D Joseph, L T Robert, C.Y Gary. Pharmacotherapy ; A
Pathophysiologic approach. 9th edition.USA. M CGraw Hill
publication2014. chapter11 Hperlipidemia, P: 291-299
REFERENCES