Atorvastatin & dyslipidemia
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Transcript of Atorvastatin & dyslipidemia
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
esVLDL &
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-cholesterol2. total-cholesterol3. ApoB lipoproteinemia
4. Familial hypercholesterolemia5. Combined hyperlipidemia6. Familial Dysbetalipoproteinemia
Lipinorm is indicated for the treatment of :
1.
1. LDL-cholesterol2. total-cholesterol3. ApoB lipoproteinemia
4. Familial hypercholesterolemia5. Combined hyperlipidemia6. 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-cholesterolApoB lipoproteinemia Familial hypercholesterolemiaCombined hyperlipidemia Familial Dysbetalipoproteinemia
Treatment
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 Profilefrom Clinical Drug Investigation [TM] 2002.