SECONDARY PREVENTIONS Jaimon Stucki MS-1 PSCOM

Blood Draw

Centrifuge

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

Where does cholesterol come from?

Deep Fried Twinkie

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

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

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

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

The Statin Decade: For LDL: “Lower is Better” R² = p < LDL Cholesterol (mg/dl) CHD Events (%) Adapted and Updated from O’Keefe, J. et al., J Am Coll Cardiol 2004;43: S CARE LIPID HPS PROVE IT –TIMI 22 TNT

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

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

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

The Statin Decade: For LDL: “Lower is Better” R² = p < LDL Cholesterol (mg/dl) CHD Events (%) Adapted and Updated from O’Keefe, J. et al., J Am Coll Cardiol 2004;43: S CARE LIPID HPS PROVE IT –TIMI 22 TNT

Simva + EZ Vytorin

The Statin Decade: For LDL: “Lower is Better” R² = p < LDL Cholesterol (mg/dl) CHD Events (%) Adapted and Updated from O’Keefe, J. et al., J Am Coll Cardiol 2004;43: S CARE LIPID HPS PROVE IT –TIMI 22 IMPROVE IT TNT

“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?

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

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