Transcript Slide 1
a By t o Magdi r v a sEl-Shalakany tatin calcium atorvastatin calcium 8 More than 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 650’000 die annually of CHD. 15 millions (5%) In Egypt, the WHO estimate for CHD is 3.5 Million. it is estimated that around 150’000 die from CHD in Egypt annually. recent hemorrhage Myocardial infarction Coronary artery atheromatous plaque Coronary artery thrombosis 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 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. Free Cholesterol Apoproteins Phospholipids Cholesterol Esters Triglycerides Diameter (nm) Density (g/ml) Protein Total lipid (%) (%) % of Lipid Fraction 90 - 1000 < 0.95 1-2 98 - 99 88 8 1 3 30 - 90 0.95 - 1.006 7 - 10 90 - 93 56 20 8 15 25 - 30 1.006 - 1.019 11 89 29 26 9 34 20 - 25 1.019 - 1.063 21 79 13 28 10 48 10 - 20 1.063 - 1.125 33 - 57 67 - 43 16 43 10 31 TG PL FC CE Lipoproteins have different sizes, different densities, different content, different apoproteins, different receptor sites, different pathways & different effects. Go lgi Lipoprotein Lipase Glucose synthesis in the liver Glycerol free fatty a Transported by serum albumin = Chylomicron Cholesterol ester Triacylglycerol Hydrophilic layer: phospholipids, FC, Apoproteins Fig 1-A There are two major ways in which dyslipidemias are classified: 1. Etiological i.e. the cause of the condition genetic (familial), or secondary (non familial). This classification can be problematic, because most conditions involve the intersection of genetics and lifestyle issues. 2. Phenotype i.e. the presentation in the body (the specific type of lipid increased). 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. Fredrickson Classification: Phenotype Type of Lipoprotein Elevated I IIa IIb Chylomicrons LDL LDL & VLDL Both Cholesterol III IV V IDL (VLDL) Triglycerides Triglycerides VLDL & chylomicrons Lipoprotein Lipase Glucose synthesis in the liver Glycerol free fatty a Transported by serum albumin = Chylomicron Cholesterol ester Triacylglycerol Hydrophilic layer: phospholipids, FC, Apoproteins Fig 1-A 1. Lipinorm is indicated for the treatment of : 1. LDL-cholesterol 4. Familial hypercholesterolemia 2. total-cholesterol 5. Combined hyperlipidemia 3. ApoB lipoproteinemia 6. Familial Dysbetalipoproteinemia 1. 2. Lipinorm is indicated for the treatment of : 1. LDL-cholesterol 4. Familial hypercholesterolemia 2. total-cholesterol 5. Combined hyperlipidemia 3. ApoB lipoproteinemia 6. Familial Dysbetalipoproteinemia Lipinorm is indicated for the Prevention of : Coronary Heart Disease in High Risk patients: • Reduces the risk of angina • Reduces the risk of myocardial infarction • Reduces the risk of stroke i.e. with multiple risk factors. Positive family history of premature vascular ds. Advancing age Male Gender or post-menopause in females Treatment Dyslipidemia HDL-C ( LDL-C or HDL-C) DM II with retinopathy, albuminuria or macroangiopathy. Smoking Hypertension 1- Prevention of Cardiovascular Disease in risk adults: • Reduces the risk of angina. Obesity • Reduces the risk of myocardial infarction. • Reduces the risk of stroke. Sedentary life 2- Treatment of Dyslipidemia: LDL-cholesterol ApoB lipoproteinemia total-cholesterol Familial hypercholesterolemia Combined hyperlipidemia Familial Dysbetalipoproteinemia NOERMAL HDL-C 40 mg % NOERMAL LDL-C 130 mg % NOERMAL Total-C 200 mg % Total/HDL Ratio (35 60) 16 weeks comparative study 16 weeks comparative study 16 weeks comparative study Frederickson's phenotype IIa Frederickson's phenotype IIb 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 IIb. 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.