secondary preventions jaimon stucki ms-1 pscom. blood draw
TRANSCRIPT
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SECONDARY PREVENTIONSJaimon StuckiMS-1 PSCOM
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Blood Draw
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Centrifuge
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Lipid Profile
Triglycerides LDL Cholesterol HDL Cholesterol Total Cholesterol Chol/HDL
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Where does cholesterol come from?
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Deep Fried Twinkie
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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
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Fenofibrate (Tricor)
Lower serum Triglycerides
Niaspan Increase HDL Flushing/Slow-
Release
Fibrates Niacin
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Statins
HMG CoA Reductase Inhibitors Atorvastatin,Lovastatin, Rosuvastatin,
Simvastatin (Zocor) Decrease LDL levels
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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
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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
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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
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Ezetimibe
Blocks a specific receptor in small intestine: reduces absorption of dietary and biliary cholesterol by 50%
Well tolerated
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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
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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
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Simva + EZ
Vytorin
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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
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“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??
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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
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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