PR3105 Lipids Management Handout Version 2012 Annotated-2

PR3105 Pharmacotherapy I
Tuesday, 7 February and Tuesday, 10 February 2012
Dyslipidemia Management
Joyce Lee, Pharm.D., BCPS, BCACP
Assistant Professor in Clinical Pharmacy
Principal Clinical Pharmacist, Ambulatory Care
Department of Pharmacy
National University of Singapore
Objectives
Understand lipid metabolism and pathophysiology of
atherosclerosis
Be able to determine lipid treatment goals by using
appropriate parameters and tests
CHD risk factors and 10-year CHD risk
Be familiar with MOH clinical practice guidelines for lipids

National Heart Lung and Blood Institute (NHLBI): Adult
Treatment Panel III (ATPIII)
Know the pharmacology of the lipid-lowering medications

Dosing
Side effects
Monitoring parameters
Be able to apply knowledge and provide individualized

pharmacologic and non-pharmacologic therapies
Cholesterol
Essential for life:
Statins CI in
pregnant women
Precursor molecule for the formation of bile

acids
Synthesis of steroid hormones
Formation of cell membranes
Obtained in two ways:

Diet (exogenous)
Intracellular synthesis through a series of
biochemical steps (endogenous)
3
Cholesterol: Lipoproteins
Large Spherical
Particles
Oily core
* Triglycerides (TG)
* Cholesterol (CH)
Hydrophilic surface
Cholesterol: Lipoproteins
Three major lipoproteins
Very-Low-Density Lipoproteins (VLDL):
transport endogenous TG and CH
VLDL = TG/2.2 if mmol/L or TG/5 if mg/dL
Focus on LDL
and TG still,
increasing HDL
not of utmost
importance
compared to
the other few
factors
HDL: transport LDL

back into the liver
High-Density Lipoproteins (HDL):

transport CH from cells to liver
Low-Density Lipoproteins (LDL):

transport endogenous CH to cells
LDL= TC (HDL+VLDL)
HDL: the good guys

TG above 4.5 level will
cover the levels of the
LDL, LDL of utmost
importance, high TG
also important, cld
cause pancreatitis
Do not use this formula if TG 4.5 mmol/L (400 mg/dL)
Other lipoproteins
Chylomicrons
LDL: the bad guys
transports whatever
you consume
transport dietary CH and TG to liver
Lipoprotein Classes and Inflammation
Chylomicrons,
VLDL, and
their catabolic
remnants
> 30 nm
HDL
LDL
HDL able to grab LDL from the

intima space and transport the
LDL into the liver, but if LDL
levels too high, then it will be
quite hard for the HDL to do this
2022 nm
Potentially proinflammatory
915 nm
Potentially antiinflammatory
Doi H, et al. Circulation. 2000;102:670-676; Colome C,

et al. Atherosclerosis. 2000;49:295-302; Cockerill GW,
et al. Arterioscler Thromb Vasc Biol. 1995;15:1987-1994.
Slide Source
Lipids Online Slide Library
www.lipidsonline.org
Cholesterol Metabolism
Cholesterol Metabolism: Made Simple

Exogenous
(chylomicrons)
Endogenous
(LDL, VLDL, HDL)
cholestrol problems not

just diet but could be due
to genetics
GOOD TO KNOW THE

TYPES
usually we just see which
cholestrol is elevated, LDL?
or TG?
Dyslipidemia
Abnormalities in lipid metabolism

Polygenic: acquired (environmental + genetic)
Familial: inherited (genetic)
Types of Dyslipidemia
Increased Concentration
Lipoprotein
Serum Lipid
LDL
Cholesterol
Mixed Dyslipidemia
LDL & VLDL
Cholesterol & TG
Hypertriglyceridemia
VLDL
TG
Hypercholesterolemia
Severe
Chylomicrons
[TG>10mmol/L (900mg/dL)]
TG
9
not primary dyslipidemia, as a result of underlying cause.

Intention shld be targetted at treating the underlying cause
Secondary Dyslipidemia
Disorder
Lipid Abnormalities
TC
example: HIV
medication
HIV is becoming
a chronic
disease. HIV
medication
prolonging the
life of patient, but
HIV medication is
very toxic and
one of the side
effects include
dyslipidemia,
therefore give
cholestrol
medication
TG
Diabetes Mellitus
Chronic renal Failure
Nephrotic syndrome
Hypothyroidism
Alcohol abuse
Cholestasis
usually type 2,
increase in TG
due to diet
Pregnancy
Drugs*
HDL
TG is elevated,
pregnant
mother's eat
more
* ex: diuretics, blockers, oral contraceptives, corticosteroids, retinoids,

anabolic steroids, progestins related to testosterone not necessary to
memorise everything
TG and/or TC, HDL
10
MOH Clinical Practice Guidelines 2/2006: Lipids
True or False
For every 1% increase in blood cholesterol levels,
there is a 1-2% increase in the incidence of
coronary heart disease (CHD).
MRFIT (Multiple Risk Factor Intervention Trial)
TRUE
N=361,662
JAMA1986; 256-2823
11
Atherosclerosis
athero = porridge-like and sclerosis =
fibrous-like
A progressive thickening and hardening
of the walls of arteries as a result of fat
deposits on their inner lining
weakening of the walls of

the arteries. walls break,
form clots, clots break up
and travel to other places
12
LDL get stuck in the inner most of the arteries, only harmful when it gets stuck in the innermost level, oxidised. Macrophage
tries to eat the oxidised LDL, but cannot digest, become foam cells.
Foam cells: Macrophages with oxidised LDL
Fatty streak: Blood vessel no longer smooth
Fatty streak becomes bigger, become atheroma
Many artheroma become a plaque, the wall is very vulnerable, can potentially rupture
if it ruptures and travels to the brain -- > Lethal
13
supply nutrient blood to

the heart, if no nutrient
blood reaches to that
part of the heart, the
heart dies
Ahh, I think I am
having a heart
attack!!
Bad Cholesterol
Atherosclerosis
Coronary Heart Disease (CHD)
14
CHD
Also known as coronary artery disease,
ischemic heart disease, and
atherosclerosis heart disease
Stroke, Heart attack, and Myocardial
Infarction
CHD equivalent conditions:

pressure
Diabetes mellitus Diabetes=blood
(hypertension)=dyslipidemia
disease in the brain
due to artherosclerosis
Atherosclerotic cerebrovascular disease,
Peripheral artery disease or Abdominal aortic
aneurysms
usually happen in elderly males, who smoke.
Aneurysms=bulging of the artery, that section of the artery will be weak and
can potentially rupture. Aorta is the largest blood vessel. Rupture, blood leaks
into the abdominal
15
MUST KNOW
Major Risk Factors for CHD

FAITH2S
Potential qns:
Given case, how
many risk
factors are
there?
Family history of premature CHD

CHD in male first degree relative < 55 years
CHD in female first degree relative < 65 years
Age
don't be
surprise if
you see a
patient with
HDL level
2mmol/l and
still has
heart
problems.
This is
because,
lab doesnt
exactly
break down
the type of
HDL present
Men 45 years
Women 55 years
slightly different from

hypertension. Take note!
Indian ethnicity ethnicity is a risk factor

TC 6.2 mmol/L (240 mg/dL) or LDL 4.1 mmol/L
(160 mg/dL)
HDL < 1.0 mmol/L (40 mg/dL)
HTN (BP 140/90 mm Hg or on anti-hypertensive
medication)
Cigarette Smoking
HDL
1.6 mmol/L (60 mg/dL) counts as a negative risk factor.
16
Major Risk Factors for CHD

FAITH2S
Family history of premature CHD
in this case, number of risk

factors = 2
3-1 (HDL negative risk factor)
CHD in male first degree relative < 55 years

CHD in female first degree relative < 65 years
Age
Men 45 years
Women 55 years
Indian ethnicity
TC 6.2 mmol/L (240 mg/dL) or LDL 4.1 mmol/L
(160 mg/dL)
HDL < 1.0 mmol/L (40 mg/dL)
HTN (BP 140/90 mm Hg or on anti-hypertensive
medication)
Cigarette Smoking
HDL
1.6 mmol/L (60 mg/dL) counts as a negative risk factor.
17
Estimation of 10-Year Coronary

Heart Disease Risk
Refers to risk of having myocardial infarction or coronary
death in the next 10 years
Modified from the Framingham-based NCEP ATPIII 10Year Risk Score Tables, USA
ATPIV to be published in 2012 (?)
Gender specific
Male vs. Female
Ethnicity-specific
(Singapore population)
Chinese
Malay
Indian
18
NO NEED TO
MEMORISE, WILL BE
GIVEN DURING EXAM
Estimation of
10-Year CHD Risk for Men
Age
Points
20-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
-9
-4
0
3
6
8
10
11
12
13
HDL
mmol/L (mg/dL)
Points
1.6 (60)
1.3-1.5 (50-59)
1.0-1.2(40-49)
<1.0(40)
-1
0
1
2
Systolic
BP (mmHg)
Points
If untreated
If treated
0
0
1
1
2
0
1
2
2
3
<120
120-129
130-139
140-159
160
Points
Smoker
Age
20-30
Age
40-49
Age
50-59
Age
60-69
Age
70-79
No
Yes
Points
TC mmol/L
(mg/dL)
Age
20-30
Age
40-49
Age
50-59
Age
60-69
Age
70-79
<4.1 (160)
4.1-5.1 (160-199)
5.2-6.1 (200-239)
6.2-7.2 (240-279)
7.3 (280)
11
1 19
Estimation of 10-Year CHD Risk for Men

10-Year Risk (%)
Total Points
Chinese
Malay
Indian
-1
<1
<1
<1
<1
<1
10
11
11
12
14
13
11
18
14
11
13
>20
15
13
17
>20
16
17
>20
>20
17
>20
>20
>20
20
Estimation of
10-Year CHD Risk for Women
Age
Points
20-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
-7
-3
0
3
6
8
10
12
14
16
HDL
mmol/L (mg/dL)
Points
1.6 (60)
1.3-1.5 (50-59)
1.0-1.2(40-49)
<1.0(40)
-1
0
1
2
Systolic
BP (mmHg)
Points
If untreated
If treated
0
1
2
3
4
0
3
4
5
6
<120
120-129
130-139
140-159
160
Points
Smoker
Age
20-30
Age
40-49
Age
50-59
Age
60-69
Age
70-79
No
Yes
Points
TC mmol/L
(mg/dL)
Age
20-30
Age
40-49
Age
50-59
Age
60-69
Age
70-79
<4.1 (160)
4.1-5.1 (160-199)
5.2-6.1 (200-239)
6.2-7.2 (240-279)
11
7.3 (280)
13
10
2 21
Estimation of 10-Year CHD Risk for Women

10-Year Risk (%)
Total Points
Chinese
Malay
Indian
<1
<1
<1
<1
<1
<1
10
11
12
13
14
15
16
10
17
12
18
10
16
19
13
20
20
16
>20
21
12
20
>20
22
15
>20
>20
23
19
>20
>20
24
>20
>20
>20
22
Don't need to know but you will know

eventually when you go out to practise
TC, LDL, HDL and TG Classifications

TC mmol/L (mg/dL)
<5.2 (200)
Desirable
HDL mmol/L (mg/dL)

<1.0 (40)
5.2-6.1 (200-239) Borderline high
1.0-1.5 (40-59)
6.2 (240)
1.6 (60)
High
LDL mmol/L (mg/dL)

<2.6 (100)
Optimal
Low
Desirable
High
TG mmol/L (mg/dL)
<1.7 (150)
Optimal
2.6-3.3 (100-129)
Desirable
1.7-2.2 (150-199)
Desirable
3.4-4.0(130-159)
Borderline high
2.3-4.4 (200-399)
High
4.1-4.8 (160-189)
High
4.9 (190)
4.5 (400)
Very high
Very high
Conversion from mmol/L to mg/dL:

TC, LDL, and HDL in mmol/L x 38.6= mg/dL; TG in mmol/L x88.5= mg/dL 23
MUST KNOW BY
HEART
Lipid Goals based on:

Three Risk Group Categories
High Risk
Group
Intermediate Risk
Group
Low Risk
Group
LDL mmol/L
(mg/dL)
<2.6
(100)
<3.4
(130)
<4.1
(160)
TG mmol/L
(mg/dL)
<2.3
(200)
<2.3
(200)
<2.3
(200)
HDL mmol/L
(mg/dL)
1.0
(40)
1.0
(40)
1.0
(40)
Non-HDL* mmol/L
(mg/dL)
<3.4
(130)
<4.1
(160)
<5.0
(190)
* Non-HDL= TC HDL (0.8 mmol/L or 30 mg/dL higher than LDL goal); mostly
VLDL
* May consider lower LDL to 1.8-2.1 mmol/L (70-80 mg/dL) with confirmed
CHD and DM or presence of other CHD risk factors (TNT study)
NCEP ATPIII Guidelines, USA
24
normally we treat LDL first, treat TG first if patient

is at risk of pancreatitis
Risk Groups Stratification:

Its As Easy As 1, 2, 3.
25
YES
Step1 Identify individuals with:

1) Established CHD eg LDL 2.6
2) CHD risk Equivalents:
Diabetes mellitus
Atherosclerotic cerebrovascular disease,
peripheral artery disease, or
abdominal aortic aneurysm
NO
Step 2 Count the Risk Factors (FAITH S):

TC6.2 (240) or LDL 4.1 (160) HDL<1.0 (40)
Cigarette smoking Indian ethnicity Age (45 yo;55 yo)
HTN (BP 140/90 or on anti-HTN meds)
Family Hx of CHD (1o relative <55 yo; 1o relative <65 yo)
2
2 Risk Factors
0-1 Risk Factor

Step 3 Estimate:
10-Year CHD risk Score
10-year CHD Risk >20% 10-year CHD Risk 10-20% 10-year CHD Risk <10%
HIGH RISK
INTERMEDIATE RISK
LOW RISK
26
Revisit Lipid Goals based on:

Three Risk Group Categories
High Risk
Group
Intermediate
Risk Group
Low Risk
Group
LDL mmol/L
(mg/dL)
<2.6
(100)
<3.4
(130)
<4.1
(160)
TG mmol/L
(mg/dL)
<2.3
(200)
<2.3
(200)
<2.3
(200)
HDL mmol/L
(mg/dL)
1.0
(40)
1.0
(40)
1.0
(40)
Non-HDL* mmol/L
(mg/dL)
<3.4
(130)
<4.1
(160)
<5.0
(190)
* Non-HDL= TC HDL (0.8 mmol/L or 30 mg/dL higher than LDL goal); mostly
VLDL
* May consider lower LDL to 1.8-2.1 mmol/L (70-80 mg/dL) with confirmed
CHD and DM or presence of other CHD risk factors (TNT study)
NCEP ATPIII Guidelines, USA
27
Dyslipidemia
Management
Nonpharmacologic
Pharmacologic
28
Nonpharmacologic:
Therapeutic Lifestyle Changes (TLC)
Quit smoking
5As: Ask, Assess, Advice, Assist, Arrange
Weight Reduction
Healthy Adult BMI: 19 to 24.9 kg/m2
BMI Formula = [wt in Kg/(height in m)2]
Exercise
4 hrs/week of moderate to vigorous aerobic and/or
resistance exercise is linked with greater CVD risk
reduction compared with lower volumes of activities
Diet Modification
must tell patient the target.

eg: What does it count as
exercise
HR needs to be increased.
Formula to calculate target
heart rate will be taught next
time during pre-reg training
dont have to memorise

Fruit, vegetables, grains, cereals, legumes
everything because we are not
Skinless poultry, fish, lean meats
dietitian, just need to know that
fiber food and lean meat is the
Low-fat dairy products
way to go
Restrict alcohol and simple carbohydrates (mainly TG)
29
Nonpharmacologic (Contd) :
Therapeutic Lifestyle Changes (TLC)
High Risk
Group
Intermediate
Risk Group
Low Risk
Group
LDL mmol/L
Goal (mg/dL)
<2.6
(100)
<3.4
(130)
<4.1
(160)
LDL mmol/L
(mg/dL) Level
at which to
Initiate TLC
2.6
(100)
3.4
(130)
4.1
(160)
Initiate TLC if LDL is above goal.

Consider Adding pharmacologic
therapy to TLC after 3 months if
LDL is still above goal.
if patient is ready to
start medication then
dont have to wait 3
mths
Unless patient has pancreatisits, LDL should be the first

one to be treated.
LDL --> TG --> Maintain
If patient is under control, is it possible to stop medication?
Usually stopping the medication will lead to increase in
LDL, the medication is usually life long.
Need to correct mind set of patient, it doesnt mean that
the more medication you take the more serious your
condition is. Explain to patient the side effects of stopping
the medication.
Clinical setting (not standard protocol) Explain30
that you
Exercise is fun!
can reduce the medication, if patient is able to prove
stability at 2 clinical parameters at 2 different time point,
you can reduce the medication dosage. Let patient be
hopeful and therefore adherent
The reality is
lifestyle modification is very challenging
31
Pharmacologic Therapy
HMG-CoA Reductase Inhibitors
Cholesterol Absorption
Inhibitor
Bile Acid Sequestrants
Nicotinic Acid
Fibric Acids
Other
Omega-3 Fatty Acids
32
Pharmacologic Therapy(Contd)
eg patient with diabetes and
heart disease, patient in high risk
gro rarely given 3 mths, but for
exam sake, just state that you
will give 3mth for patient to
decrease their LDL levels
High Risk Group
Intermediate Risk
Group
Low Risk Group
<2.6
(100)
<3.4
(130)
<4.1
(160)
3.4
(130)
[2.6-3.3 (100-129)
drug optional]
10-year risk 10-20%:

3.4
(130)
5.0
(190)
[4.1-4.9 (160-189)
drug optional]
10-year risk <10%:
4.1
(160)
require aggressive
treatment
LDL mmol/L
GOAL (mg/dL)
LDL mmol/L
(mg/dL) Level
at which to
Consider Drug
Therapy*
* TLC should also be initiated (if the patients have not started it already) or
continued (if the patients have started it already).
Therapeutic Lifestyle Changes
Diet, exercise, smoking etc
33
Pharmacologic Therapy:
HMG-CoA Reductase Inhibitor
statins
Life saving
medication
1. Beta
blockers
2. HMG-CoA
reductase
inhibitor
3. Aspirin
same MOA
Six me-too drugs

fluvastatin, lovastatin, pravastatin, simvastatin,
atorvastatin, rosuvastatin
actually got 7,
7th medication is
pitastatin, but not
approved in
Singpaore yet
MUst know all 6
The only class of lipid-lowering agents

consistently demonstrating reduction in overall
if patient is contraindicated for this
mortality
medication, has drug allergy etc
Have to put it down but before
this down into the patient
Primary Use: lower LDL (up to 60%) putting
file, you have to be very sure. Statin
Mixed Dyslipidemia
medication is a very important and

life saving drug
if patient has pancreatitis, Statin is not

the first line drug to try to reduce TG
since it is only effective in reducing
34
LDL levels
Lipid Lowering
Effects of
Statins*
Statin
Dose (mg)
LDL (%)
HDL (%)
TG (%)
Fluvastatin
20
40
80
22
25
35
3
4
6
12
14
18
Lovastatin
20
40
80
27
31
42
6
5
8
10
14
19
Pravastatin
10
20
40
80
22
32
34
37
7
2
12
3
15
11
24
19
Simvastatin
20
40
80
38
41
47
11
9
8
15
18
24
Atorvastatin
10
20
40
80
39
43
50
60
6
9
6
5
19
26
29
37
Rosuvastatin
5
10
20
40
43
50
53
62
13
14
8
15
35
37
37
40
* Pitavastatin (Livalo) approved by FDA in 2010; Not yet registered in Singapore.
35
qns to think about:

ACEI are also me too
drugs, same MOA and
same potency, reason
being to control the price of
the drug. Create
competition among the
drug companies
Statin Potency
The first medication to be

given to lower LDL should
be the dose required to
reduce the LDL level to the
optimal level. This is unlike
anti-hypertensive drugs
which needs to be titrated
slowly
different statin has

different potency
Adapted from The STELLAR Study: Am J Cardio 2003; 92:152-60; pitavastatin package insert 2010.
36
trick to memorise is:

Diagonal
Have to know patient's
baseline control, table
will only work if you
know the patient's
baseline
HMG-CoA Reductase Inhibitor (Contd)
MUST KNOW, MUST KNOW THE
CONVERSION OF THE DIFFERENT
STATIN, WILL COME OUT FOR
EXAMS
+6x1
+6x2
+6x3
+6x4
RULE OF SIX*
Approx.
LDL (%)
fluva
(mg)
lova/prava
(mg)
simva
(mg)
atorva
(mg)
30
40
20
10
36
80
40
20
10
80
40
20
10
80
40
20
80
40
42
48 (up to 50)
54 (up to 60)
rosuva
(mg)
* For each doubling of statin dose, LDL decreases by additional ~6% from
BASELINE
37
Adapted and modified from Steve Chen, PharmD, FASHP, CDM, USC School of Pharmacy 8/07
HMG-CoA Reductase Inhibitor (Contd)
Rule of Six may be applied if the baseline LDL is
known
often in newly diagnosed cases
When the baseline LDL is not known, the

percent of LDL reduction must be estimated
Method 1: use rule of six to ballpark
look at the previous
reduction,
when you double
Method 2: look at the trends; predict the LDL the dose, the
amt of
reduction based on the LDL reduction from thereduction will be the same
previous dose increase
Keep in mind that diet and exercise will also

contribute to the LDL reduction to an extend
The degree of LDL reduction vary from person to
person
38
Case: Lets find that dose

Big Mac is a 55 yo Chinese with DM. He
has a baseline LDL of 2.9 mmol/L (112
mg/dL). His doctor would like to start him
on rosuvastatin 5 mg today. Big Mac,
however, cannot afford rosuvastatin and
would like to take simvastatin instead. His
doctor consults you for a dose.
What is your recommendation?
target LDL level: 2.6 because patient belongs to high risk

5 rosuva=20 simva which will bring about 36% decrease of LDL which will reduce to
1.9mmol/L, dose might be too high, too potent greater side effect.
What if we give simvastatin 10mg
30% reduction from baseline ~2.0mmol/L, use 10 or even 5mg of simvas might be
enough
39
HMG-CoA Reductase
Inhibitor: Mechanism
of Action (MOA)
Cholesterol Synthesis Cascade
HMG-CoA reductase
catalyzes the rate limiting
step in hepatic
intracellular cholesterol
synthesis
The Inhibition indirectly
causes increased cellular
uptake of LDL molecules
and lower the
intravascular (blood)
circulating LDL
concentration effectively.
40
HMG-CoA Reductase Inhibitor: Dosing

Fluva
Lova
Prava
Simva
Atorva
Rosuva
Dose (mg)
20, 40, 80
20, 40, 80
10, 20, 40, 80
20, 40, (80)
10, 20, 40, 80
5, 10, 20, 40
Special
dosing
requirement
N/A but
should also
take
special
precaution
when
combined
with other
lipid
lowering
agents
*Not to
exceed 20mg
if comb w/
niacin
1g/day,
gemfibrozil,
cyclosporine,
danazol
*Not to
exceed 40mg
if comb w/
verapamil,
amiodarone
N/A but
should also
take special
precaution
when
combined
with other
lipid lowering
agents
*Not to exceed
10mg if
combined with
amiodarone,
verapamil,
diltiazem; not
to exceed
20mg with
amlodipine,
ranolazine; C/I
with
gemfibrozil,
cyclosporine
N/A, but
should also
take special
precaution
when
combined
with other
lipid lowering
agents
*Not to
exceed 5mg
if comb w/
cyclosporine
*Not to
exceed
10mg if
comb
w/gemfibrozil
but not w/
fenofibrate
if increase is less than

3X, can continue giving
patient the medication,
level of AST or ALT will
usually NORMALISE
Hepatic
Renal
If AST or ALT progress to 3 x the UNL and persist, dose reduction or drug withdrawal is
recommended AST, ALT liver function test. ALT more specific for liver. AST produced in liver, skin,
Not
Needed
brain
initial dose
x 50% if CrCl
<30ml/min,
titrate to
response
initial dose
x 50% if CrCl
<60ml/minm,
titrate to
response
initial dose x
50% if CrCl
<30ml/minm,
titrate to
response
Not needed
Initial dose
5mg and
max dose
10mg if CrCl
<30ml/min
May increase dose slowly (benefit vs. risk) with close monitoring. Low initial dose also recommended
41
for other statins with unspecified max dose. Usually treat with statin AGGRESSIVELY,titrate dose
slowly only if patient has renal disease, slowly
monitoring
Simvastatin Labeling Change

(June 2011)
FDA change, max dose for

simvastatin should be 40mg not
80mg since a study done prove
that patient on 80mg will
experience stronger side effect
Exception:
patient can
continue the
80mg max dose
if
42
http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm (accessed 5 August 2011)
HMG-CoA Reductase Inhibitor:

Adverse Effects
Few adverse drug reactions
Discontinuation rate comparable to placebo
GI distress (2-4%; most common, but mild)
Abdominal pain, constipation, flatulence, dyspepsia
statin
Hepatotoxicity (0.1-2.3%; rare and dose-dependent)
overwork the
liver
Resolve upon discontinuation of statin within 2-3
months
other medication which will overwork the liver too
Prevention: Avoid EtOH and other hepatotoxic agents
Other minor adverse reactions: rash, headache, sleep
disturbances (anxiety, irritability)
43
Circulation 2002;106; 1024-1028

Adverse Effects (contd)
Myopathy (0.2%, rare but can
be serious): ANY muscle
CK unlike ALT is not specific, usually not
Access the patient. ASk
disease
done. Exercise can result in CK increasing
patient more specific qns, ask
muscular
disease,
seperated into 3
different
categories
too.
Myalgia: Muscle ache/weakness; no CK

Myositis: Muscle symptoms with 10 x ULN of CK
Male: ULN= 200 IU/L and Female: ULN= 150 IU/L
Rhabdomyolysis
IRREVERSIBLE
Marked CK >10 x ULN AND creatinine elevation

Risk factors,
must know,
important for
exams
Usually brown urine with myoglobin
them where is the pain. Statin

induced myopathy results in
generalised pain. Co-relate
with timeline of when patient
start the dose. Ask patient if
their muscle pain is getting
better. IF yes, then most
probably not myopathy
because in myopathy, muscle
pain will worsen
At risk if: high dose, old age, renal impairment, and/or LDL-lowering
agent combination therapy (with nicotinic acid, fibrates)
Myopathy management:
If due to stain: Discontinue statin in any patient who develops
myopathy or in CK +/- fever or malaise
If not sure about the cause: May stop statin or lower the dose if
patient with muscle pain and without CK
44
* Abbreviations: CK: creatinine kinase; ULN: upper limit of normal
outcomes: 80mg more potent

than 20mg
Improvement of morality and
morbidity quite similar.
45
Lancet 2010;376:1658-69
Based on SEARCH* Study
looking at ALT
probably not too

sure
truly know for
sure
* Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH)

46
Lancet 2010;376:1658-69

Contraindications
ACTIVE Liver disease
Hepatitis, cirrhosis, hepatic encephalopathy
Alcoholism
Pregnancy Category: X
Cholesterol biosynthesis is important for fetal
dose may not affect baby that much BUT that
development low
doesnt mean can give low dose. Statin CI in
Breast-feeding
pregnant mothers regardless of the dose
47
Good to know.
Take for example: patient is
experencing nightmares.
Choose a more philic
medication.

Relevant PK, PD, and Interactions
fluva
lova
prava
simva
atorva
rosuva
Lipophilicity*
phobic
philic
phobic
philic
philic
phobic
Elimination
CYP2C9
CYP3A4
Hepatic
sulfation
CYP3A4
CYP3A4
CYP2C9
(only 10%)
May
digoxin
level x 20%
May
warfarin
effect
Separate
from
Antacid
May
warfarin
effect
Separate
from
Antacids
Increased
[plasma] in
Japanese
& Chinese
Drug
Interaction
May
May
cyclosporine warfain
or phenytoin effect
May
digoxin level
x 20%
warfarin
effect
Separate
from antacids
Few drug
interaction
Separate
from
Antacids
May
digoxin
level x
20%
May
warfarin
effect
Food
interaction
With or
without
Must take
with food
With or
without
With or
without
With or
without
With or
without
Time of
intake
Evening
Evening
Anytime
Evening
Anytime
Anytime
48
* lipophobic statins are less likely to cross BBB; may be associated w/less insomnia (<3% incidence)

Significant Drug Interactions
CYP3A4 Inducers
( lova, simva, atorva)
CYP3A4 Inhibitors
( lova, simva, atorva)
Phenytoin, phenobarbital, barbiturates,

rifampin, danazol, carbamazepine, St.
Johns Wort
Antiretroviral protease inhibitors,
amiodarone, azol antifungal agents* ,
erythromycin*, clarithromycin*,
troleandomycin*, telithromycin*,
nefazadone, cyclosporine, verapamil,
diltiazem, grapefruit juice
* Reduce statin dose x 50% when given with these medications

[Note: agents with are contraindicated with simvastatin (new June 2011)]
Pravastatin undergoes hepatic sulfation, no effect on

CYP450 system does not go thru CYP450 system
Fluvastain: metabolized by CYP2C9 enzyme system;
less drug interactions overall
49

Monitoring
Check LFT at baseline, 6-12 weeks after initiation or
dose increase then at least once annually
Stop statin if LFT >3xUNL; may reintroduce statin at lower dose
when LFT normalize
Baseline CK not necessary; check if symptoms of

myopathy present (with or without risk for
Rhabdomyolysis)
Stop statin if CK > 5-10x UNL with muscle pain
Rosuvastatin: Routine urineanalysis especially at high

dose (i.e. 40 mg)
Associated with dose-related proteinuria
Chinese and Japanese subjects have 2-fold higher plasma
concentration compared to other ethnic groups
50

Selection Consideration
Benefit of statins appear to be a class
effect
Consider LDL goal and potential drug
interactions when selecting statin
Initial dose often = dose needed for
desired % LDL reduction
Beneficial to ALL secondary prevention
patients regardless of baseline LDL
51
Cholesterol Absorption Inhibitor
Ezetimibe
Only one strength
(e.g.10 mg)
Primary Use: lower

LDL
Available as a combo
drug with simvastatin
(e.g. Vytorin)
usually given when patient cannot tolerate statin
Almost dont need any monitoring
52
Cholesterol
Absorption
Inhibitor: MOA
Selectively blocks
absorption of
dietary and biliary
cholesterol through
intestinal wall
works locally
53
Cholesterol Absorption Inhibitor (Contd)

Lipids lowering effects:
Ezetimibe: not
as potent and
very costly
Things to think
abt:
Potentcy vs
cost
Ezetimibe
Ezetimibe +
statin
synergistic effect
LDL (%)
HDL (%)
TG (%)
19
Additional
7-19
Additional
2
Additional
11
- Provide up to 19% additional LDL lowering effects vs. 6% with

doubling statin dose
Dosing:
only one strength

available
Ezetimibe 10 mg orally every day with or without food

No dose adjustment for elderly, renal insufficiency, mild hepatic
impairment
Ezetimibe/simvastatin: 10/10mg, 10/20mg, 10/40mg, and (10/80mg)

One tablet orally every night with or without food
LDL, HDL and TG by 45-60%, 6-10%, and 23-31%, respectively
54

Adverse Effects:
Well tolerated (adverse events similar to placebo)
Although cases of myopathy and rhabdomyolysis have
been reported
Incidence of diarrhea (3.7%) slightly higher

compared to placebo (3%)
Contraindications: None known
Drug Interactions:
12-fold ezetimibe level observed in 1 patient
receiving cyclosporine
Require close monitoring in patients taking cyclosporine
Take 2 hours before or 4 hours after resins (studied

in cholestyramine)
55

Monitoring Parameter
Routine laboratory testing not necessary
Very Safe
Due to localized activity in GI
Selection Consideration:
Consider for patients unresponsive or intolerant to
other medications
Keep in mind selection considerations for statins if
combined
Pregnancy Category: C
56
Fibric Acids
Gemfibrozil and
fenofibrate
not the first
Primary Use: Lower
drug of
choice
unless
TG
patient has
TG and you
have to
lower TG
first
Mixed dyslipidemia
Severe
hypertrigliceridemia
Isolated low HDL
One of the drug preferred to take
away once patient stabilise. Recall:
risk factors of myopathy
57
Fibric Acids: MOA

Unclear
Inhibit triglyceride synthesis
Increase lipoprotein lipase activity which
catabolizes chylomicrons and VLDL TG and LDL
Increase HDL through improved Apo A-I and
Apo A-II synthesis
lipoprotein lipase: enzyme
required to lyse
Fibrate
Serum VLDL (TG rich)
Lowered serum VLDL (TG)
58
Fibric Acids (Contd)

Lipid Lowering Effect
Fenofibrate is more effective in lowering LDL
compare to gemfibrozil
Fibrates not used to
lower LDL
Fibrates will
remove VLDL,
there is more
cholestrol in the
blood, therefore
transient increase
in LDL
LDL* (%)
5-25
HDL (%)
10-20
TG (%)
20-50
*LDL may increase if TG is very high SUPER HIGH
DO NOT
MEMORISE THE
NUMBERS
Ex: if LDL is low [e.g. <2.6 mmol/L (100 mg/dL)] and TG is

very high [e.g. >11.4-17.0 mmol/L (1,000-1,500 mg/dL)], LDL
will likely to 2.6-3.2 mmol/L (100-120 mg/dL) in response to
fibrate
LDL by 30% if TG > 9.1 mmol/L (800 mg/dL)
LDL by 5-22% if TG 3.4-9.1 mmol/L (300-800 mg/dL)
If LDL 3.9 mmol/L (150 mg/dL), consider adding another
lipid lowering agent to LDL
59

Dosing*
Fibric Acids
only one type of
gemfibrozil
many types of
fenofibrate
Gemfibrozil
Administration
600 mg bd. Max 1200 mg/day. Take 30 minutes
before breakfast and dinner.
Fenofibrate** Initially: 100 mg orally tds or 300 mg om with food.

(Trolip)
Maintenance: 100 mg orally bd with food. Max:
100 mg qds with food.
* Gemfibrozil 1,200 mg = Fenofibrate 300 mg
** Different formulation available; check dose for each brand name
Fibrates: Start with

the low dose. Try
not to give with
statin, if needed
give low dose of
fibrates because it
increases the risk of
myopathy
*you dont want
patient to think that
they can eat
anything they want
and not control their
TG levels from diet
Adverse Effects
Most common: nausea, dyspepsia, abdominal pain
Less common: rash, cholelithiasis, myositis,
hepatitis/liver enzyme elevation (~7.5% incidence)
60

Contraindication
Very rare side effect: If patient has had gallstone problems before, may need
to take caution being giving patient the fenofibrate. If have to give, give low
dose. MOA: increase in cholestrol secreted in bile --> Gallstone
*wont come out during exam, question is too vague
Pre-existing gallbladder disease

hepatic dysfunction
severe renal disease
fibrate may start to accumulate at CrCl < 50ml/min
Monitoring parameter
Regular LFT checks
Check bilirubin and creatine kinase if myopathy
suspected
Pre-existing gallbladder disease, hepatic dysfunction,
severe renal disease
61
FYI will be recovered in year 4

Drug interaction
warfarin level; may need to warfarin dose by up to
30%
Whenever possible
choose fenofibrate Gemfibrozil inhibits CYP2C8 (e.g. rosiglitazone,
over gemifibrozil
repaglinide)
Statin: combination therapy may risk of myopathy
Controlled clinical trials (n=600)
Low-to-moderate dose statin w/ fibrate has a low risk of
myopathy
1% incidence of CK >3xULN w/o myalgia
Most data are with lovastatin and gemfibrozil
Interaction most problematic w/ gemfibrozil

Inhibition of hepatic glucuronidation (not fenofibrate)
J Am Col Cardiol 2002;40(3):568-79
JAMA 2003;289:1681-1690
62
Fibric Acids:
Fenofibrate is better tolerated, slightly
more potent, and has less drug interaction
compared to gemfibrozil
Gemfibrozil has known increased risk of
rhabdomyolysis with statins
Preliminary data suggest no inhibition of
glucuronidation with fenofibrate
63
Good to know medication, hardly

used
Bile Acid Sequestrants
resins
Cholestyramine
Rarely used due to
side effects
Primary use: Lower

LDL (up to 30%)
A low-potency agent
For mild cases only
May increase TG
64
Bile Acid Sequestrants: MOA

Resins bind to bile
acid in intestines
Bile acids exit body via
feces
Liver coverts more
cholesterol into bile acids
which exit body via feces
Result: lower
cholesterol
more cholestrol used to make bile acid
therefore lower cholestrol
65
Bile Acid Sequestrants (contd)

Lipid lowering effects
LDL (%)
HDL (%)
TG (%)
15-30
3-5
10-15 (especially if with

pre-existing TG)
Dosing:
dosing no need to know
Cholestyramine (powder)
Initial: 4 g (1 packet) 1-2x/day
Max: 24 g/day
Adverse Effects (20-30%, most common):

Abdominal fullness, gas, constipation, bloating,
nausea, dyspepsia
most common side effect
if patient has a
problem of
constipation and on
OTC therefore
cannot be given
Take with at least 180 ml of water to minimize constipation

In general, GI adverse drug reactions can be minimized
through slow titration of dose
66
Bile Acid Sequestrants (contd)

Common Drug Interactions:
MANY (due to binding by resins)
Absorption of many drugs (e.g. warfarin, digoxin,
thyroxine, thiazide diuretics, statins, -blockers, fat
soluble vitamins, folic acid)
Separate administration of interacting drugs
(2 hours before or 6 hours after resins)
Monitoring parameter
Routine laboratory testing not required
Very Safe!
not usually
monitored just
like the one in
ezetimibe
Routine laboratory testing not required

67
Bile Acid Sequestrants (contd):

Generally used for mild LDL elevations or in
combination with a statin for further LDL
lowering
Relatively contraindicated in patients with high
TG >4.5 mmol/L (>400 mg/dL) or severe
constipation
Seldomly used in patients with DM
DM patients tend to have TG
May need to start with low doses and try
different preparations (if available) to improve
tolerance
68
Nicotinic Acid
Different formulations
available
Immediate release
Prolonged release
Primary Use: HDL and

TG
Mixed dyslipidemia
Severe
hypertriglyceridemia
Isolated low HDL
Prefered to give fibrates rather than nicotinic acid.
NIcotinic acid --> less tolerated more side effects
69
FYI GOOD TO KNOW
Nicotinic Acid: MOA
you cant tell

which APO
A1, could
be APO A1,
A2, A3
70
Curr Atheroscler Rep. 2000;2:36-46
Nicotinic Acid (Contd)

Lipid lowering effects
Compare and contrast with fibrate
Formulation
LDL (%)
HDL (%)
TG (%)
Immediate Release
6-25
15-35
20-50
Prolonged Release
5-14
18-22
21-28
Dosing
Formulation
Dose range/day
Titration
Immediate Release
1.5-6.0 g
Many ways. Key point: titrate slowly.

Ex: starting at 100 mg tds with meals,
by 300 mg/wk to max dose of 6 g/day
divided bd to tds.
Prolonged Release
1.0-2.0 g
500 mg at bedtime with low-fat snack,

dose x 500 mg no sooner than every
4 wks to max dose of 2 g/day.
71
**** NO NEED TO KNOW THE DOSE BUT NEED TO KNOW THE DIFFERENCES
BETWEEN PROLONGED AND IMMEDIATE RELEASE
Prolonged release could improve compliance, need no take so frequently
PG induced vasodilator
Vasodilate and make face red, in severe case could
be itchy
Immediate release more common for this side
effect, most of the time flushing and pruritus occur
in the initial phase
To help patient: Can recommend to patient to take
aspirin or NSAIDS (will inhibit PG synthesis), take
low dose
In cardiac patient, aspirin is given to thin out the
blood therefore you may not even need to give the
aspirin

Adverse Effects
Flushing, pruritus upon initiation or dose increase

Titrate slowly and take with food
Take Aspirin 100-300 mg 30-60 min prior to administration
GI distress, gastritis
Titrate slowly and take with food
Hepatotoxicity
Usually when daily dose > 2-3 g; keep dose as low as
possible
Less common with immediate release formulation
More common in
prolonged release
formulation. Stay in
system longer, more toxic
effect
Chance of hepatoxicity
increases with more lipid
lowering agents
dependent on patient's initial uric acid level. If patient's

Hyperuricemia uric
acid level is high this cld be a potential problem
Hyperglycemia
ADMIT Study (1.8 mmol/L, FBG; 0.3% A1C)

This medication is avoided in patient who are obsese and at risk for pre-diabetic
condition, avoid because drug may cause hyperglycemia
72

Contraindications
Liver disease, active PUD
GERD, DM, gout (relative contraindications)
if gout is uncontrolled,
definitely cannot be given.
The other conditions GERD
and DM usually not given
because patient cannot
tolerate
Drug Interactions
Statin: concurrent use may risk of myopathy, but not
as much as fibrate-statin combo.
Adrenergic blocking agents: additive vasodilation may
induce postural hypotention
Antioxidants (Vit. C&E, -carotene, selenium) may
interfere with HDL-raising effects of niacin
HDL increase seems to be affected
73
Nicotinic Acid (Contd):

Drug of choice for increasing HDL
Not first line treatment in patients with diabetes,
gout or history of GERD
Titration may be labor-intensive for some patients
Assess patients competency
Prolonged release is better tolerated than

immediate release
Flushing is most troublesome but tachyphylaxis usually
develops after several days
74
Omega-3 Fatty Acids
OTC or prescription
Fish Oil [eicosapentaenoic acid (EPA) +

docosahexaenoic acid (DHA)]
MOA: Inhibit hepatic TG synthesis
Primary Use: lower TG (up to 25-30%)
MOH Clinical Practice Guidelines recommend
adding fish oil in severe hypertriglyceridemia
[TG >10 mmol/L (900 mg/dL)], where fibrates
alone may not adequately lower the markedly
elevated TG level.
For younger patient: Try fibrates first before trying fish oil
BUT
For older patient: who are on statin, give fish oil or give fibrates? Give fish oil. Giving fibrates
plus statin plus patient's age --> at risk for rhabdomyolsis
75
Omega-3 Fatty Acids

Population
AHA Recommendations
Patients without Eat a variety of (preferably oily) fish at least twice/week.

documented CHD Include oils & foods rich in -linolenic acid (flaxseed,
canola, and soybean oils, walnuts)
Patients with
Consume ~1g of EPA+DHA/day, preferably from oily fish.
documented CHD EPA+DHA capsules could be considered in consultation
with MD.
Patients who
need to TG
2-4g of EPA+DHA/day provided as capsules under MD

care.
Oily Fish
Non-Oily Fish
Trout
Haddock, Cod, tinned tuna
salmon
Fresh Tuna
76
Omega-3 Fatty Acids (Contd)

Side effects
GI distress (4.9%)
Nausea (1.4%)
Fishy aftertaste/ burp: common at higher
doses
Clinical bleeding (very rare at doses <3 g/day)
Usually when taking together with agents that may
thin the blood
Caution in
Increased blood glucose (may occur with

doses >3 g/day in patients with DM or
impaired glucose tolerance)
patient wio
are taking
warfarin and
aspirin.
Ok to take if
patient is on
baby
77 dose of
aspirin
Omega-3 Fatty Acids:

Pregnant women should avoid large predator
fish (shark, swordfish, tilefish, king mackerel,
limited tuna)
Mostly due to mercury content and other pollutants in
big fish
Consider risk vs. benefit when it comes to

selecting fibrates vs. fish oil to treat patients with
elevated TG
Risk of myopathy?
How severe is the patients TG?
Can TG be controlled with diet and exercise?
Drug interactions?
CVD
Fish oil is effective for CD
risk reduction
78
Dyslipidemia Management Recap
Types of
Dyslipidemia**
Hypercholesterolaemia
Lipoprotein
Serum Lipid
LDL
Cholesterol
Drug of Choice
Statin +/Ezetimibe
Mixed Dyslipidemia
LDL & VLDL
Cholesterol & TG Statin +/- fibrate*

Fibrate* +/- statin
VLDL
TG
Fibrate*
(or fish oil?)
Severe
[TG>10mmol/L
(900mg/dL)]
Chylomicrons
TG
Fibrate* + fish oil
* nicotinic acid can also be considered

** Isolated low HDL: may consider fibrate or nicotinic acid
79
Dyslipidemia Management Recap
Types of
Dyslipidemia**
Hypercholesterolaemia
Lipoprotein
Serum Lipid
LDL
Cholesterol
Drug of Choice
Statin +/Ezetimibe
Mixed Dyslipidemia
LDL & VLDL
Cholesterol & TG Statin +/- fibrate*

Fibrate* +/- statin
VLDL
TG
Fibrate*
(or fish oil?)
Severe
[TG>10mmol/L
(900mg/dL)]
Chylomicrons
TG
Fibrate* + fish oil
* nicotinic acid can also be considered

** Isolated low HDL: may consider fibrate or nicotinic acid
80
For patient who have achieved goal, the monitoring frequency
Lipids Monitoring Frequency

Performance parameter
All patients on lipid
modifying drug therapy
(not achieving LDL goal)
Patients who are not on
lipid modifying drug
therapy and/or goal LDL
levels achieved
Recommended lipid profile

monitoring frequency
At least every 6-12 months
High Risk
Every 1 year
Intermediate
Risk
Every 2 years
Low Risk
Every 3 years
Definitely want to
try to discharge
patient after 6mths
Full effect takes
place in 3mth
(more common to
do test in 3mth
rather than 6
weeks)
6 weeks: Enough
for minimal
reduction in LDL
(Dont try to
overcompensate)
Precautions:
10-12 hrs of fasting needed for the estimation of TG
Defer tests for 2wks after a febrile illness
CH level may be depressed between 24hr to 3 mo after an acute MI
81
Dyslipidemia Management: Special

Consideration for Special Population
Diabetes Mellitus
CHD risk equivalent
Often present with metabolic syndrome*
Risk Factor
Abdominal Obesity
Men
Women
dont need to know

the definition but
need to know the
type of risk factors
Defining Level
Waist Circumference
>90cm
>80cm
Triglycerides
HDL
Men
Women
1.7 mmol/L (150mg/dL)
Blood Pressure
130/85 mmHg or on BP med
Fasting glucose
6.1 mmol/L (110mg/dL)
<1.0 mmol/L (40mg/dL)

<1.3 mmol/L (50mg/dL)
*Clinical identification of Metabolic Syndrome any 3 of the above
82
Will be covered in DM lecture

Consideration for Special Population (Contd)
ADA Guidelines: Dyslipidemia in Type 2 DM*
No Overt CVD At risk for stroke
Primary goal: LDL <100 mg/dL (<2.6 mmol/L)
>40 yo: give statin to achieve 30-40% LDL
regardless of baseline LDL
<40yo but CV risk due to other risk factors: meds
suggested to reach lipid goals
Overt CVD already had stroke

All patients: given stain to achieve 30-40% LDL
Evidence suggest high-dose statin therapy to achieve
LDL goal of < 70 mg/dL (1.8 mmol/L)
* Note on the changes in ADA 2010; see DM lecture.
83

Children
Drug therapy should only be considered in children 12
years of age with:
Severe familial hypercholesterolemia, AND
after failing to achieve LDL <4.9 mmol/L (190 mg/dL) after
dietary intervention
vs adults: LDL<2.6
Statin may be used in children with proper monitoring

Resins may be added to statin if LDL goal not
achieved Resins ok because children usually dont take much
Elderly
medication therefore no drug-drug interaction
Age is not contraindicated to drug therapy if indicated

Drug therapy Decision based on: at risk for stroke already
10-year CHD Risk Score
Life-expectancy and quality of life
84

Women
Pre/postmenopausal: therapy decision based
on 10-Year CHD Risk Score
Pregnant
Treatment only indicated if severe
hypertiglyceridemia [TG>10 mmol/L (900 mg/dL)]
only omega-3 fish oil recommended after dietary
intervention
Statin contraindicated
Pregnancy Category: X
85

Renal Disease
Use low statin dose in chronic renal failure
Use low fibrate dose if indicated and renal failure is mild to
moderate
Fibrates are contraindicated if CrCL <10 ml/min
Monitor CK and renal function and symptoms of myopathy

closely
Liver Disease
Screen liver function on 2 consecutive occasions in patients with
chronic liver disease due to alcohol abuse or hepatitis B
Low dose statin or fibrates may be given if AST and/or ALT is
elevated but < 3x UNL
Monitor CK, liver function and symptoms of myopathy closely
86
Dyslipidemia Treatment Summary

Review Lipid Panel
Yes
risk of pancreatitis
TG >4.5mmol/L (400mg/dL)
Determine LDL goal
No
* CHD or CHD equivalent

* Risk factors
Reach TG goal
Initiate or modify
drug therapy to reach
TG <4.5mmol/L
(<400mg/dL)
No
Yes
Yes
Reach non-HDL Goal

(intensify LDL lowering drug
or add fibrate/nicotinic acid
to further VLDL)
No
Yes
statin
resin
ezetimibe
* 10-year CHD risk score
Reach LDL Goal

(initiate or modify
drug therapy)
if patient
cannot cut
oily
No down
food
Determine need to
treat TG
Initiate or modify drug therapy
If TG 2.3-4.5mmol/L
(200-399mg/dL)
Treat low HDL

if HDL <1mmol/L (40mg/dL)
No
Yes
87
give
fenofibr
ate,
omega
3 or ask
patient
to cut
down
oily food
To read on your own
Common Dyslipidemia Management Errors

Not receiving lipid lowering drug therapy when
indicated
Inadequate dosing of lipid-lowering drug therapy
(particularly statins); lack of follow up of lipid
panels
No treatment plan for elevated TG
High-risk drug combinations (e.g. gemfibrozil)
Patient unaware of how to monitor for or
manage adverse effects
Non-compliance, if you give statins LDL level should
drcrease, if it doesnt can suspect non-compliance
88
Conclusion
Dyslipidemia is asymptomatic
20-25% of patients present with death as their first sign of CAD
Patients should be educated and reminded of the

potential adverse effects, drug/food interactions and
timing of dose of lipid modifying medications
Diet and exercise (as tolerated) should always
accompany lipid modifying medications
Fenofibrate may be safer than gemfibrozil when
combined with a statin
Niacin can be used for patients with diabetes
Fish oil is very effective for TG and CHD risk but is
underutilized
Max dose of simvastatin is 40 mg ON; may continue with
80 mg ON only if taken for 12 months with no
symptoms of muscle toxicity.
89
Questi ns?
Thank you.
Dr. Joyce Lee

Email: phalycj@nus.edu.sg
90

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PR3105 Pharmacotherapy I

Tuesday, 7 February and Tuesday, 10 February 2012

Be familiar with MOH clinical practice guidelines for lipids

Know the pharmacology of the lipid-lowering medications

Be able to apply knowledge and provide individualized

Precursor molecule for the formation of bile

Obtained in two ways:

HDL: transport LDL

High-Density Lipoproteins (HDL):

Low-Density Lipoproteins (LDL):

HDL: the good guys

Do not use this formula if TG 4.5 mmol/L (400 mg/dL)

LDL: the bad guys

transport dietary CH and TG to liver

Lipoprotein Classes and Inflammation

HDL able to grab LDL from the

Doi H, et al. Circulation. 2000;102:670-676; Colome C,

Cholesterol Metabolism: Made Simple

cholestrol problems not

GOOD TO KNOW THE

Abnormalities in lipid metabolism

LDL & VLDL

not primary dyslipidemia, as a result of underlying cause.

Chronic renal Failure

* ex: diuretics, blockers, oral contraceptives, corticosteroids, retinoids,

weakening of the walls of

supply nutrient blood to

CHD equivalent conditions:

Major Risk Factors for CHD

Family history of premature CHD

slightly different from

Indian ethnicity ethnicity is a risk factor

1.6 mmol/L (60 mg/dL) counts as a negative risk factor.

Major Risk Factors for CHD

in this case, number of risk

CHD in male first degree relative < 55 years

1.6 mmol/L (60 mg/dL) counts as a negative risk factor.

Estimation of 10-Year Coronary

Estimation of 10-Year CHD Risk for Men

Estimation of 10-Year CHD Risk for Women

Don't need to know but you will know

TC, LDL, HDL and TG Classifications

HDL mmol/L (mg/dL)

5.2-6.1 (200-239) Borderline high

LDL mmol/L (mg/dL)

Conversion from mmol/L to mg/dL:

Lipid Goals based on:

normally we treat LDL first, treat TG first if patient

Risk Groups Stratification:

Step1 Identify individuals with:

Step 2 Count the Risk Factors (FAITH S):

0-1 Risk Factor

Revisit Lipid Goals based on:

must tell patient the target.

dont have to memorise

Initiate TLC if LDL is above goal.

Unless patient has pancreatisits, LDL should be the first

High Risk Group

Low Risk Group

10-year risk 10-20%:

Six me-too drugs

The only class of lipid-lowering agents

medication is a very important and

if patient has pancreatitis, Statin is not