SECONDARY PREVENTIONSJaimon StuckiMS-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

CholesterolSynthesis

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.

CholesterolSynthesis

SynthesizedCholesterol ≈50% of

IntestinalCholesterolIs Absorbed

Transport viaHDL-C and LDL-C

(≈75%)

Chylomicron Transport

Biliary Cholesterol Transport

Fecal Sterols

DietaryCholesterol(≈25%)

ExtrahepaticOrgans

Liver Intestine

LDL-C IDL-C VLDL-C

Fenofibrate (Tricor)

Lower serum Triglycerides

Niaspan Increase HDL Flushing/Slow-

Release

Fibrates Niacin

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

CholesterolSynthesis

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.

CholesterolSynthesis

SynthesizedCholesterol ≈50% of

IntestinalCholesterolIs Absorbed

Transport viaHDL-C and LDL-C

(≈75%)

Chylomicron Transport

Biliary Cholesterol Transport

Fecal Sterols

DietaryCholesterol(≈25%)

ExtrahepaticOrgans

Liver Intestine

LDL-C IDL-C VLDL-C

The Statin Decade:The Statin Decade:For LDL: “Lower is Better”For LDL: “Lower is Better”

0

5

10

15

20

25

30R² = 0.9029R² = 0.9029p < 0.0001p < 0.0001

LDL Cholesterol (mg/dl)

CH

D E

ven

ts (

%)

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

Cholesterol Levels Are Affected by Multiple Organ Systems

Net Cholesterol Balance in Humans

LDL Receptors

CholesterolSynthesis

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.

CholesterolSynthesis

SynthesizedCholesterol ≈50% of

IntestinalCholesterolIs Absorbed

Transport viaHDL-C and LDL-C

(≈75%)

Chylomicron Transport

Biliary Cholesterol Transport

Fecal Sterols

DietaryCholesterol(≈25%)

ExtrahepaticOrgans

Liver Intestine

LDL-C IDL-C VLDL-C

Ezetimibe

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

Well tolerated

1% 0%

–2%

–18%*

–8%*

1%*

–20%

–15%

–10%

–5%

0%

5%

LDL-C TG (median) HDL-C

Mean %Change

FromUntreated

Baseline

placebo (n=431)

ezetimibe 10 mg (n=1,288)

Clinical Studies with Ezetimibe Monotherapy

*P0.01 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:The Statin Decade:For LDL: “Lower is Better”For LDL: “Lower is Better”

0

5

10

15

20

25

30R² = 0.9029R² = 0.9029p < 0.0001p < 0.0001

LDL Cholesterol (mg/dl)

CH

D E

ven

ts (

%)

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

Simva + EZ

Vytorin

The Statin Decade:The Statin Decade:For LDL: “Lower is Better”For LDL: “Lower is Better”

0

5

10

15

20

25

30R² = 0.9029R² = 0.9029p < 0.0001p < 0.0001

LDL Cholesterol (mg/dl)

CH

D E

ven

ts (

%)

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 ITIMPROVE IT66665252

TNT

“Is (Even) Lower (Even) Better ?”

Can Eze/Simva lower LDL to a greater Can Eze/Simva lower LDL to a greater degree than standard treatment (Simva degree than standard treatment (Simva 40 mg) and by doing so 40 mg) and by doing so reduce major reduce major cardiovascular eventscardiovascular events??

Eze/Simva Surrogate and Clinical Outcome Program

TrialTrial PopulationPopulation EndpointEndpoint TreatmentTreatment

ENHANCEENHANCEHeFHHeFH

(n = 720)(n = 720)Carotid IMTCarotid IMT

Eze/Simva 10/80 Eze/Simva 10/80 vsvs

Simva 80Simva 80

IMPROVE-ITIMPROVE-ITACSACS

(n = 10,000)(n = 10,000)MACEMACE

Eze/Simva 10/40 Eze/Simva 10/40 vsvs

Simva 40Simva 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