1. SECONDARY PREVENTIONS Jaimon Stucki MS-1 PSCOM

2. Blood Draw

3. Centrifuge

4. Lipid Profile  Triglycerides  LDL Cholesterol  HDL Cholesterol  Total Cholesterol  Chol/HDL

5. Where does cholesterol come from?

6. Deep Fried Twinkie

7. Cholesterol Levels Are Affected by Multiple Organ Systems Net Cholesterol Balance in Humans LDL Receptors Cholesterol Synthesis LDL and Other Receptors IDL-C = intermediate-density lipoprotein cholesterol; VLDL-C = very low-density lipoprotein cholesterol. Turley SD et al. Prev Cardiol. 2003;6:29–33, 64; Dietschy JM. Am J Clin Nutr. 1997;65(suppl): 1581S–1589S, adapted with permission by the American Journal of Clinical Nutrition. © Am J Clin Nutr. American Society for Clinical Nutrition. Cholesterol Synthesis Synthesized Cholesterol ≈50% of Intestinal Cholesterol Is Absorbed Transport via HDL-C and LDL-C (≈75%) Chylomicron Transport Biliary Cholesterol Transport Fecal Sterols Dietary Cholesterol (≈25%) Extrahepatic Organs LiverIntestine LDL-C IDL-CVLDL-C

8.  Fenofibrate (Tricor)  Lower serum Triglycerides  Niaspan  Increase HDL  Flushing/Slow-Release FibratesNiacin

9. Statins  HMG CoA Reductase Inhibitors  Atorvastatin,Lovastatin, Rosuvastatin, Simvastatin (Zocor)  Decrease LDL levels

10. Cholesterol Levels Are Affected by Multiple Organ Systems Net Cholesterol Balance in Humans LDL Receptors Cholesterol Synthesis LDL and Other Receptors IDL-C = intermediate-density lipoprotein cholesterol; VLDL-C = very low-density lipoprotein cholesterol. Turley SD et al. Prev Cardiol. 2003;6:29–33, 64; Dietschy JM. Am J Clin Nutr. 1997;65(suppl): 1581S–1589S, adapted with permission by the American Journal of Clinical Nutrition. © Am J Clin Nutr. American Society for Clinical Nutrition. Cholesterol Synthesis Synthesized Cholesterol ≈50% of Intestinal Cholesterol Is Absorbed Transport via HDL-C and LDL-C (≈75%) Chylomicron Transport Biliary Cholesterol Transport Fecal Sterols Dietary Cholesterol (≈25%) Extrahepatic Organs LiverIntestine LDL-C IDL-CVLDL-C

11. The Statin Decade: For LDL: “Lower is Better” R² = 0.9029 p < 0.0001 LDL Cholesterol (mg/dl) CHD Events (%) Adapted and Updated from O’Keefe, J. et al., J Am Coll Cardiol 2004;43:2142-6. 30 50 70 90 110 130 150 170 190 210 4S CARE LIPID HPS PROVE IT –TIMI 22 TNT

12. Cholesterol Levels Are Affected by Multiple Organ Systems Net Cholesterol Balance in Humans LDL Receptors Cholesterol Synthesis LDL and Other Receptors IDL-C = intermediate-density lipoprotein cholesterol; VLDL-C = very low-density lipoprotein cholesterol. Turley SD et al. Prev Cardiol. 2003;6:29–33, 64; Dietschy JM. Am J Clin Nutr. 1997;65(suppl): 1581S–1589S, adapted with permission by the American Journal of Clinical Nutrition. © Am J Clin Nutr. American Society for Clinical Nutrition. Cholesterol Synthesis Synthesized Cholesterol ≈50% of Intestinal Cholesterol Is Absorbed Transport via HDL-C and LDL-C (≈75%) Chylomicron Transport Biliary Cholesterol Transport Fecal Sterols Dietary Cholesterol (≈25%) Extrahepatic Organs LiverIntestine LDL-C IDL-CVLDL-C

13. Ezetimibe l Blocks a specific receptor in small intestine: reduces absorption of dietary and biliary cholesterol by 50% l Well tolerated

14. Clinical Studies with Ezetimibe Monotherapy *P  0.01 vs placebo. Pooled Results From 2 Multicenter, Double-Blind, Placebo-Controlled, 12-Week Studies in 1,719 Patients With Primary Hypercholesterolemia Source: Ezetimibe package insert

15. The Statin Decade: For LDL: “Lower is Better” R² = 0.9029 p < 0.0001 LDL Cholesterol (mg/dl) CHD Events (%) Adapted and Updated from O’Keefe, J. et al., J Am Coll Cardiol 2004;43:2142-6. 30 50 70 90 110 130 150 170 190 210 4S CARE LIPID HPS PROVE IT –TIMI 22 TNT

16. Simva + EZ Vytorin

17. The Statin Decade: For LDL: “Lower is Better” R² = 0.9029 p < 0.0001 LDL Cholesterol (mg/dl) CHD Events (%) Adapted and Updated from O’Keefe, J. et al., J Am Coll Cardiol 2004;43:2142-6. 30 50 70 90 110 130 150 170 190 210 4S CARE LIPID HPS PROVE IT –TIMI 22 IMPROVE IT 66 52 TNT

18. “Is (Even) Lower (Even) Better ?” Can Eze/Simva lower LDL to a greater degree than standard treatment (Simva 40 mg) and by doing so reduce major cardiovascular events?

19. Eze/Simva Surrogate and Clinical Outcome ProgramTrialPopulationEndpointTreatment ENHANCEHeFH (n = 720) Carotid IMT Eze/Simva 10/80 vs Simva 80 IMPROVE-ITACS (n = 10,000) MACE Eze/Simva 10/40 vs Simva 40

20. Drug Cost  Fenofibrate 200mg$69/30 day  Lovastatin 40mg$36/30 day  Atorvastatin 20mg (Lipitor)$120/30 day  Simvastatin 40mg (Generic)$28/30 day  Ezetimibe 10mg (Zetia)$100/30 day  Vytorin 40/10mg$108/30 day