SECONDARY PREVENTIONS Jaimon Stucki MS-1 PSCOM. Blood Draw.
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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
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