Secondary Preventions
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Transcript Secondary Preventions
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
Extrahepatic
Organs
Liver
LDL-C
Intestine
IDL-C
VLDL-C
Dietary
Cholesterol
(≈25%)
LDL Receptors
Biliary Cholesterol Transport
(≈75%)
Transport via
HDL-C and LDL-C
LDL and
Other
Receptors
Chylomicron Transport
Synthesized
Cholesterol
Cholesterol
Synthesis
Cholesterol
Synthesis
≈50% of
Intestinal
Cholesterol
Is Absorbed
Fecal Sterols
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.
Fibrates
Fenofibrate (Tricor)
Lower serum
Triglycerides
Niacin
Niaspan
Increase HDL
Flushing/Slow-Release
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
Extrahepatic
Organs
Liver
LDL-C
Intestine
IDL-C
VLDL-C
Dietary
Cholesterol
(≈25%)
LDL Receptors
Biliary Cholesterol Transport
(≈75%)
Transport via
HDL-C and LDL-C
LDL and
Other
Receptors
Chylomicron Transport
Synthesized
Cholesterol
Cholesterol
Synthesis
Cholesterol
Synthesis
≈50% of
Intestinal
Cholesterol
Is Absorbed
Fecal Sterols
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.
The Statin Decade:
For LDL: “Lower is Better”
30
R² = 0.9029
p < 0.0001
25
4S
20
CHD Events (%)
LIPID
CARE
15
HPS
TNT
10
PROVE IT –TIMI 22
5
0
30
50
70
90
110
130
150
170
190
210
LDL Cholesterol (mg/dl)
Adapted and Updated from O’Keefe, J. et al., J Am Coll Cardiol 2004;43:2142-6.
Cholesterol Levels Are Affected by Multiple Organ
Systems
Net Cholesterol Balance in Humans
Extrahepatic
Organs
Liver
LDL-C
Intestine
IDL-C
VLDL-C
Dietary
Cholesterol
(≈25%)
LDL Receptors
Biliary Cholesterol Transport
(≈75%)
Transport via
HDL-C and LDL-C
LDL and
Other
Receptors
Chylomicron Transport
Synthesized
Cholesterol
Cholesterol
Synthesis
Cholesterol
Synthesis
≈50% of
Intestinal
Cholesterol
Is Absorbed
Fecal Sterols
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.
Ezetimibe
Blocks a specific receptor in small intestine: reduces
absorption of dietary and biliary cholesterol by
50%
Well tolerated
Clinical Studies with Ezetimibe Monotherapy
Pooled Results From 2 Multicenter, Double-Blind, Placebo-Controlled,
12-Week Studies in 1,719 Patients With Primary Hypercholesterolemia
LDL-C
5%
1%
TG (median)
HDL-C
1%*
0%
0%
Mean %
Change
–5%
From
Untreated –10%
Baseline
–2%
–8%*
–15%
–20%
–18%*
placebo (n=431)
ezetimibe 10 mg (n=1,288)
*P0.01 vs placebo.
Source: Ezetimibe package insert
The Statin Decade:
For LDL: “Lower is Better”
30
R² = 0.9029
p < 0.0001
25
4S
20
CHD Events (%)
LIPID
CARE
15
HPS
TNT
10
PROVE IT –TIMI 22
5
0
30
50
70
90
110
130
150
170
190
210
LDL Cholesterol (mg/dl)
Adapted and Updated from O’Keefe, J. et al., J Am Coll Cardiol 2004;43:2142-6.
Simva
+
Vytorin
EZ
The Statin Decade:
For LDL: “Lower is Better”
30
R² = 0.9029
p < 0.0001
25
4S
20
CHD Events (%)
LIPID
CARE
15
HPS
TNT
10
PROVE IT –TIMI 22
5
52
66
IMPROVE IT
0
30
50
70
90
110
130
150
170
190
210
LDL Cholesterol (mg/dl)
Adapted and Updated from O’Keefe, J. et al., J Am Coll Cardiol 2004;43:2142-6.
“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 Program
Trial
ENHANCE
IMPROVE-IT
Population
HeFH
(n = 720)
ACS
(n = 10,000)
Endpoint
Treatment
Carotid IMT
Eze/Simva 10/80
vs
Simva 80
MACE
Eze/Simva 10/40
vs
Simva 40
Drug Cost
Fenofibrate 200mg
Lovastatin 40mg
Atorvastatin 20mg (Lipitor)
Simvastatin 40mg (Generic)
Ezetimibe 10mg (Zetia)
Vytorin 40/10mg
$69/30 day
$36/30 day
$120/30 day
$28/30 day
$100/30 day
$108/30 day