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Ezetimibe And Lipids - Dr Vivek Baliga Reviews

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Dr Vivek Baliga reviews Ezetimibe and its role in lipid management. Just a quick overview on how this drug is effective.

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Ezetimibe And Lipids - Dr Vivek Baliga Reviews

  1. 1. Lipid Management and Ezetimibe Dr Vivek Baliga Consultant Baliga Diagnostics Pvt Ltd
  2. 2. Introduction •  Lipid-lowering therapy in patients with hypercholesterolemia has a proven survival benefit for both primary prevention (ie, in patients without clinical evidence of coronary disease) and secondary prevention (ie, in patients with established coronary disease), even when serum cholesterol concentrations are "normal"
  3. 3. Methods of action • Regression of atherosclerosis • Plaque stabilization • Reduced inflammation – Reduction in CRP – Reduction in Serum Amyloid A • Decreased thrombogenicity • Reversal of endothelial dysfunction • Reduction in ventricular arrhythmias
  4. 4. Anti-Hyperlipidemic agents • Statins – HMG CoA reductase Inhibitors • Ezetimibe • Bile acid sequestrants – Cholestyramine, colestipol • Nicotinic acid • Neomycin • Estrogen replacement therapy
  5. 5. Drug class Serum LDL Serum HDL Serum TG HMG CoA reductase inhibitors ↓ 20 to 60 percent ↑ 5 to 10 percent ↓10 to 33 percent Ezetimibe ↓ 17 percent No change No change Bile acid sequestrants ↓ 15 to 30 percent 0 to slight increase No change Nicotinic acid ↓ 10 to 25 percent ↑ 15 to 35 percent ↓ 25 to 30 percent
  6. 6. Ezetimibe • Cholesterol absorption inhibitors • Impair dietary and biliary cholesterol absorption at the brush border of the intestine without affecting the absorption of triglycerides or fat soluble vitamins • Mechanism of action may involve Niemann-Pick C1 like 1 (NPC1L1) protein or an associated protein involved in cholesterol transport
  7. 7. Ezetimibe: Clinical effectiveness1 • Elevated levels of LDL-C are highly correlated with the risk of CVD • Reducing LDL-C is associated with a reduced risk of CV events in people with, or at high risk of, CVD • Doubling the dose of statin reduces baseline LDL-C by ~6% • Switching to an alternative statin reduces baseline LDL-C by ~8% • Greater reductions of LDL-C, up to 23.2% post-statin baseline are seen when ezetimibe added to statin therapy • Ezetimibe co-administered with a statin was found to have a similar adverse event profile compared with statin therapy alone 1. National Institute for Health and Clinical Excellence. Ezetimibe for the treatment of primary (heterozygous-familial and non-familial) hypercholesterolaemia. Technology Appraisal Guidance 132. November 2007.
  8. 8. Primary Prevention
  9. 9. Other Lipid Lowering Methods
  10. 10. Secondary Prevention
  11. 11. Other Lipid Lowering Methods For Secondary Prevention
  12. 12. ACS
  13. 13. Local Derbyshire Guidance
  14. 14. Cholesterol balance: absorption and synthesis20,21 Circulation Dietary intake ~300-700 mg/day Small bowel absorption ~700 mg/day Biliary excretion ~1,000 mg/day Faecal loss 650-850 mg/day Liver synthesis ~800 mg/day hepherd J. Eur Heart J Supplements 2001;3:E2-E5. ays H. Expert Opin Invest Drugs 2002;11:1587-1604.
  15. 15. Intestinal wall Plasma Liver BileIntestinal lumen 3H-DPM(x10–6) Ezetimibe: Low Systemic Effects van Heek M et al. Br J Pharmacol 2000;129:1748-1754. 3-h post 3 H ezetimibe IV dosing 0 1 2 3 4
  16. 16. hsCRP ENHANCE Simva Eze-Simva MedianpercentchangefromBaseline p < 0.01 3 6 12 18 24 Months 10 -10 -20 -30 -40 -50 -60 -70 -80 0 -26 % incremental reduction Baseline 24 months (mg/L) (mg/L) Simva 1.7(0.8-4.1) 1.2(0.6-2.4) Eze-Simva 1.7(0.8-3-9) 0.9(0.5-1.9)
  17. 17. Pleiotropic Effects of Statins: Benefit Beyond Cholesterol Reduction? A Meta-Regression Analysis
  18. 18. LDL-C Reduction Comparisons
  19. 19. HDL-C Comparisons
  20. 20. Patients Reaching LDL-C 1.8mmol/l
  21. 21. Patients Reaching LDL-C 1.8 mmol/l – Type 2 Diabetes
  22. 22. Safety Data
  23. 23. Ezetimibe with simvastatin27 Significantly greater LDL-C reduction than simvastatin alone -60 -50 -40 -30 -20 -10 0 Mean%changeinLDL-C Simva (10 mg) n=137 -27 -44 -45 -53 -57 -36 -36 -44 Statin + placebo Statin + ezetimibe 10 mg o.d. avidson MH, McGarry T, Bettis R et al, for the Ezetimibe Study Group. J Am Coll Cardiol 2002;40:2125-2134. n=668 p≤0.01 for all parameters Simva (20 mg) n=130 Simva (40 mg) n=138 Simva (80 mg) n=132
  24. 24. Ezetimibe with atorvastatin28 Significantly greater LDL-C reduction than atorvastatin alone -60 -50 -40 -30 -20 -10 0 Mean%changeinLDL-C -35 -50 -54 -54 -60 -40 -43 -51 allantyne C, Houri J, Notarbartolo A et al for the Ezetimibe Study Group. Circulation 2003;107:2409-2415. Atorva (10 mg) Atorva (20 mg) Atorva (40 mg) Atorva (80 mg) Statin + placebo Statin + ezetimibe 10 mg o.d. n=628 p<0.01 for all parameters
  25. 25. Questions?

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