By Magdi El-Shalakanya t o r v a s t a t i n c a l c i u m

a t o r v a s t a t i n c a l c i u m

More than 8 million people die from CHD, every year worldwide, more than cancer, infectious diseases or any other causes.

In the U.S. alone, the prevalence of CHD is around 15 millions (5%) 650’000 die annually of CHD.

In Egypt, the WHO estimate for CHD is 3.5 Million. it is estimated that around 150’000 die from CHD in Egypt annually.

More than 8 million people die from CHD, every year worldwide, more than cancer, infectious diseases or any other causes.

In the U.S. alone, the prevalence of CHD is around 15 millions (5%) 650’000 die annually of CHD.

In Egypt, the WHO estimate for CHD is 3.5 Million. it is estimated that around 150’000 die from CHD in Egypt annually.

Myocardial infarction

atheromatous plaque

Coronary artery

thrombosis

recent hemorrhage

Coronary artery

Positive family history of premature vascular ds. Advancing age Male Gender or post-menopause in females Dyslipidemia ( LDL-C or HDL-C) DM II Smoking Hypertension Obesity Sedentary life

Homocysteinemia. Hypertriglyceridemia lipoprotein (a) Lpa. Small dense LDL phenotype. Insulin Resistance & hyperinsulinism. Underlying inflammation & infection. WBC. Oxidative stress & iron Overload. fibrinogen.

Positive family history of premature vascular ds. Advancing age Male Gender or post-menopause in females Dyslipidemia ( LDL-C or HDL-C) DM II Smoking Hypertension Obesity Sedentary life

Positive family history of premature vascular ds. Advancing age Male Gender or post-menopause in females Dyslipidemia ( LDL-C or HDL-C) DM II Smoking Hypertension Obesity Sedentary life

DM II predisposes to both premature onset & severity of atherosclerosis in coronary arteries CHD.

CHD is the commonest cause of morbidity & mortality in DM II.

Five of the treatable and preventable risk factors for CHD are obesity, sedentary life, hypertension, smoking & dyslipidemia.

Management of dyslipidemia is primarily carried out through lifestyle modifications then drug therapy.

In recent years, more emphasis has been focused on the management of cholesterol.

cholesterol.

FUNCTIONS OF CHOLESTEROL Structure of cell membrane Precursor of Steroid

Hormones Precursor of Bile Acids

Cholesterol & Lipoproteins.

Triglycerides

Apoproteins

Cholesterol Esters

Free Cholesterol

Phospholipids

Diameter(nm)

90 - 1000

30 - 90

25 - 30

20 - 25

10 - 20

Density(g/ml)

< 0.95

0.95 - 1.006

1.006 - 1.019

1.019 - 1.063

1.063 - 1.125

Protein(%)

1 - 2

7 - 10

11

21

33 - 57

Total lipid(%)

98 - 99

90 - 93

89

79

67 - 43

% of Lipid FractionTG PL FC CE

88

56

29

13

16

8

20

26

28

43

1

8

9

10

10

3

15

34

48

31

Lipoproteins have different sizes, different densities, different content, different apoproteins, different receptor sites, different pathways & different effects.

Go lgi

Cholesterol ester

Transported by serum albumin

Lipoprotein Lipase

Glycerol free fatty aGlucose synthesis in the liver

Fig 1-ATriacylglycerol

= Chylomicron

Hydrophilic layer: phospholipids, FC, Apoproteins

This classification can be problematic, because most conditions involve the intersection of genetics and lifestyle issues.

This classification points to the problem, the type of lipoprotein & the specific blood lipid increased as well as the treatment of choice for that specific error.

PhenotypeType of

Lipoprotein Elevated

I IIa

IIb III IV V

Chylomicrons

LDL

LDL & VLDL

IDL (VLDL) Triglycerid

es

VLDL & chylomicrons

1. Etiological i.e. the cause of the condition genetic (familial), or secondary (non

familial).

2. Phenotype i.e. the presentation in the body (the specific type of lipid increased).

Fredrickson Classification:

Cholesterol Triglycerides

Both

There are two major ways in which dyslipidemias

are classified:

Cholesterol ester

Transported by serum albumin

Lipoprotein Lipase

Glycerol free fatty aGlucose synthesis in the liver

Fig 1-ATriacylglycerol

= Chylomicron

Hydrophilic layer: phospholipids, FC, Apoproteins

1. LDL-cholesterol

2. total-cholesterol

3. ApoB lipoproteinemia

4. Familial hypercholesterolemia

5. Combined hyperlipidemia

6. Familial Dysbetalipoproteinemia

Lipinorm is indicated for the

treatment of :

1.

1. LDL-cholesterol

2. total-cholesterol

3. ApoB lipoproteinemia

4. Familial hypercholesterolemia

5. Combined hyperlipidemia

6. Familial Dysbetalipoproteinemia

Lipinorm is indicated for the

treatment of :

1.

Lipinorm is indicated for the

Prevention of :

2.

Coronary Heart Disease in High Risk

patients:

i.e. with multiple risk factors.• Reduces the risk of angina

• Reduces the risk of myocardial infarction

• Reduces the risk of stroke

Positive family history of premature vascular ds. Advancing age Male Gender or post-menopause in females Dyslipidemia ( LDL-C or HDL-C) DM II Smoking Hypertension Obesity Sedentary life

Positive family history of premature vascular ds. Advancing age Male Gender or post-menopause in females Dyslipidemia ( LDL-C or HDL-C) DM II Smoking Hypertension Obesity Sedentary life

Positive family history of premature vascular ds. Advancing age Male Gender or post-menopause in females Dyslipidemia ( LDL-C or HDL-C) DM II Smoking Hypertension Obesity Sedentary life

with retinopathy, albuminuria or macroangiopathy.

HDL-C

1- Prevention of Cardiovascular Disease in risk adults: • Reduces the risk of angina. • Reduces the risk of myocardial infarction.• Reduces the risk of stroke.

2- Treatment of Dyslipidemia: LDL-cholesterol total-cholesterol

ApoB lipoproteinemia Familial hypercholesterolemia

Combined hyperlipidemia Familial Dysbetalipoproteinemia

Treatme

nt

Total/HDL Ratio

NOERMAL HDL-C 40 mg %NOERMAL LDL-C 130 mg

%

NOERMAL Total-C 200 mg %

(35 60)

16 weeks comparative study

16 weeks comparative study

16 weeks comparative study

Frederickson's phenotype II a

Frederickson's phenotype II b

A significant proportion of patients switching from atorvastatin to

simvastatin received a low dose in terms of efficacy -lower than that

which can achieve the therapeutic goal- which may have an adverse

impact on patients' healthcare quality and probability of vascular

morbidities and mortality.

Switching from more expensive brand name drugs to generic

equivalents may reduce aggregate prescription costs.

Therapeutic benefit may not be compromised if the patient is

switched to a generic with an equivalent therapeutic profile.Reference: Gregory Hess, Therapeutic Dose Assessment of Patient Switching from Atorvastatin to Simvastatin (Am J Manag Care. Jun 2007; suppl 3; vol 13:S80-S85)

By the end of the first 16-week period, when patients in both groups

were on the 10 mg/day dose, 10 of the 15 patients on atorvastatin

(66%) presented a LDL-C level <130 mg/dl, while only 4 of the 15

patients on simvastatin (27%) achieved this goal.

Atorvastatin in equipotent doses to simvastatin appeared to be

more effective than the latter in reducing triglyceride and plasma

fibrinogen in patients with hypercholesterolaemia, and also in those

with Frederickson's phenotype II b.

Regarding HDL-C, it was increased by simvastatin only with the

20mg dose: 7% vs. baseline vs. atorvastatin; 4% at the 10mg dose

and 5% at the 20mg dose vs. baseline.

Reference: Atorvastatin vs. Simvastatin on Lipid Profile

from Clinical Drug Investigation [TM] 2002.