MANAGEMENT OF DYSLIPIDEMIA:
WHEN STATIN ALONE IS INSUFFICIENT!
Sompongse Suwanwalaikorn, MD
Options to achieve low LDL-C targets

Use maximal doses of currently
available statins

Consider new mega-statins

Consider combination therapy
Simvastatin Efficacy in Familial Hypercholesterolemia
Simvastatin
10 mg
12.2 %
0.2
Simvastatin
20%
8%
10%
0.1
0%
0
LDL
Trig
HDL
-0.1
-10%
LDL
Trig
HDL
-20%
-0.2
-40%
-30%
-0.4
randomized, double blind study, N = 110 pts. LDL 251 mg/dl;
Trig 168 mg/dl; HDL 50 mg/dl
Simvastatin
20%
-15%
-30%
14.5%
-0.3
40 mg
11%
10%
-50%
-38%
randomized, double blind, placebo controlled study N = 2221
pts. LDL 188 mg/dl; TG 132 mg/dl; HDL 45 mg/dl
20%
Simvastatin
80 mg
10%
10%
0%
0%
LDL
-10%
HDL
-10%
-30%
-30%
-40%
-40%
-50%
-43%
Nutr Metab Cardiov Dis 1998;8:135-143;
Clin Drug Invest 1995;10:127-138
4S Study. Lancet 1994;344:1383-1389
LDL
HDL
TG-1
TG-2
-20%
-20%
-50%
20 mg
-24 %
-48.4%
-38%
-60%
randomized, double blind study N = 355 LDL 240 mg/dl; Trigl 159
mg/dl (TG-1); HDL 48.6 Subgroup of pts with triglycerides 200-350
mg/dl (TG-2, N = 83)
IDEAL Trial:
Safety & Tolerability Profile in Real World
Parameter
Simvastatin
20/40mg
(n = 4,449)
Atorvastatin
40/80mg
(n = 4,439)
P value
Any adverse event resulting in
permanent discontinuation of
study drug
186 (4.2%)
426 (9.6%)
<.001
2 (0.04%)
18 (0.41%)
<.001
5 (0.11%)
43 (0.97%)
<.001
AST ≥ 3 X ULN
at 2 consecutive measurements
ALT ≥ 3 X ULN
at 2 consecutive measurements
Down-titration to atorvastatin 40mg (from Atorvastatin 80mg) due to
adverse events: 587 (13%)
JAMA, Nov 16, 2005-Vol 294, No. 19
Adverse event withdrawal rates of statins
Br J Cardiol 2004
Myopathy in association with statins is
dose-related
Br J Cardiol 2004
Options to achieve low LDL-C targets

Use maximal doses of currently
available statins

Consider new mega-statins

Consider combination therapy
8
LDL Reduction by Individual Statins
5 mg
10 mg
Fluvastatin
20 mg
40 mg
21%
24%
80 mg
Lovastatin
21%
24%
30%
Pravastatin
22%
32%
34%
30%
35%
41%
47%
39%
43%
50%
60%
52%
58%
69%
Simvastatin
22%
Atorvastatin
Rosuvastatin
45%
In general, doubling dose = additional 6% reduction in LDL
Source: Gau G, Mayo Clinic Cardiovascular Review
40%
Percentage of Patients Reaching Goal with
Starting Dose and after First Titration
Initial dose
First titration
% Patients reaching goal
60
53%
50
39%
40
32%
31%
30
22%
20
10%
10%
10
1%
0
Atorvastatin
(n=78)
Simvastatin
(n=76)
Lovastatin
(n=78)
Fluvastatin
(n=76)
Adapted from Brown AS J Am Coll Cardiol 1998;32:665–672.
LDL-C reduction across statin dose ranges in
the STELLAR study
Br J Cardiol 2004
Change in HDL-C across statin dose
ranges in the STELLAR study
Options to achieve low LDL-C targets

Use maximal doses of currently
available statins

Consider new mega-statins

Consider combination therapy
13
Theoretical Basis for Combination Rx
 Multiple pathogenetic pathways of
cholesterol in development of CAD
 Differential effects of various lipid-
lowering agents:
 Act on different pathways
 Target different lipid particles
Net Cholesterol Balance in Humans
Indications for Combination Rx
 Treatment goals not met with single agent
 Risk of intolerance, toxicity, or adverse drug
 interactions with higher dose of single
agent
 Perceived benefit from ≥ 2 agents due to
complementary:
• Mechanisms of action
• Effects on different lipids
• Effects on CHD risk
Agents Commonly Used in Combination
with Statins
 Bile acid sequestrants
 PPAR agonists (fibrates)
 Fish oils
 Niacin
 Ezetimibe
17
Agents Commonly Used in Combination
with Statins
 Bile acid sequestrants
 PPAR agonists (fibrates)
 Fish oils
 Niacin
 Ezetimibe
Bile Acid Sequestrants: Favorable Lipid
Effects of Colesevelam with Statins
% Change vs Statin Alone
Colesevelam
Statin
TC
LDL-C
HDL-C
TG
2300 mg
(~4 tablets)
Lovastatin
10 mg
–7
–12 to –10
–3 to –1
–8 to +4
2300 mg
(~4 tablets)
Simvastatin
20 mg
–6
–8
–3
0
3750 mg
(6 tablets)
Simvastatin
10 mg
–9
–16
+7
+5
3750 mg
(6 tablets)
Atorvastatin
10 mg
–4
–10
+3
+23
Bays H, et al. Expert Opin Pharmacother. 2003;4:779-790.
Agents Commonly Used in Combination
with Statins
 Bile acid sequestrants
 PPAR agonists (fibrates)
 Fish oils
 Niacin
 Ezetimibe
PPAR- Agonists (Fibrates) and Statins

Combination may significantly improve TG, LDL-C,
and HDL-C levels

Fibrates plus statins associated with increased
risk for myopathy and rhabdomyolysis
 Probably not due to cytochrome P450 drug
interaction

Gemfibrozil may impair glucuronidation of statins

Fenofibrate may have relatively less potential for
impairment of statin metabolism
Ballantyne CM, et al. Arch Intern Med. 2003;163:553-564.
Bays H. Am J Cardiol. 2002;90:30K-43K. Bays HE, et al. Expert Opin Pharmacother. 2003;4:1901-1938.
Adding Fibrate to Statin Rx Improves Profile of
Atherogenic Dyslipidemia in Patients with Metabolic
Sydrome
simvastatin
fenofibrate
simvastatin+fenofibrate
*†
*†
*
†
Mean ratio
large/small LDL
Mean mg/dL
* P ≤0.05 vs. placebo; † P ≤0.05 vs. simvastatin alone
Vega. Am J Cardiol. 2003;91:956.
Percentage of patients reaching ADA
lipid targets
Atorvastatin 20 mg
Fenofibrate 200 mg
Atorvastatin 20 mg + Fenofibrate 200 mg
% of patients reaching ADA goals
120
97.5
100
80
92.5
100
75
80
60
60
40
30
17.5
20
5
0
LDL
TG
Diabetes Care 2002;25:1198-1202
HDL
Clinical Trials of Fibrates  Statins
 FIELD (Fenofibrate Intervention and
Event Lowering in Diabetes)

9,000 patients with diabetes

Fenofibrate vs. placebo
 No statistically significant difference in the primary
composite endpoint of CHD death or nonfatal MI.

A significant reduction in nonfatal MI
 ACCORD (Action to Control
Cardiovascular Risk in Diabetes)

5800 patients with type 2 diabetes in fibrate substudy

Fenofibrate + statin vs. placebo + statin

Study completion - 2010
FIELD. Available at: http://www.cvm.controlled-trials.com/content/2/5/218.
Accessed March 2, 2005. ACCORD. Available at: http://www.accordtrial.org/public/index.cfm. Accessed March 2, 2005.
PPAR- Agonists (TZDs) and Statins
 Metabolic effects of TZDs may be
complementary to lipid-altering effects of
statins:
 Increased LDL-C particle size
 Reduced TG levels (with pioglitazone)
 Increased HDL-C levels (with pioglitazone and
rosiglitazone)
 Number of LDL particles
 Unchanged with pioglitazone
 Potentially worsened with rosiglitazone
Bays HE. Br J Diabetes Vascular Dis. 2003;3:356-360.
Ginsberg HN. Am J Cardiol. 2003;91:29E-39E.
Agents Commonly Used in Combination
with Statins
 Bile acid sequestrants
 PPAR agonists (fibrates)
 Fish oils
 Niacin
 Ezetimibe
Fish Oils and Statins
 Marine fish oils rich in omega-3 fatty acids:
• Lower TG levels
• May be alternative to fibrate plus statin
 Other CV effects complementary to statins:
• Reduction in malignant ventricular dysrhythmias
• Increased heart rate variability
• Antithrombotic effects
• Improved endothelial reactivity/relaxation
• Anti-inflammatory effects
• Slight lowering of blood pressure
Bays HE, et al. Expert Opin Pharmacother. 2003;4:1901-1938.
Kris-Etherton PM, et al. Circulation. 2002;106:2747-2757.
27
Commercial Fish Oil Preparations
 Capsules available containing >1000 mg omega-
3 fatty acids, including:

Eicosapentaenoic acid (EPA)

Docosahexaenoic acid (DHA)
 TG benefits usually associated with combined
dose of EPA + DHA of 4 g/d to 9 g/d
 Side effects include fishy aftertaste and
dyspepsia
 Inconsistent reports of early, short-lived,
potential increase in blood glucose levels in
patients with diabetes mellitus
Bays HE, et al. Expert Opin Pharmacother. 2003;4:1901-1938.
Kris-Etherton PM, et al. Circulation. 2002;106:2747-2757.
Fish Oil and Hematologic Factors
 May impair platelet aggregation and
increase bleeding time
 Potentially reduces risk for thrombosis
 Concomitant use with anticoagulants
(aspirin or warfarin):
 No significant increase in risk of bleeding
in clinical trials
Bays HE, et al. Expert Opin Pharmacother. 2003;4:1901-1938.
Kris-Etherton PM, et al. Circulation. 2002;106:2747-2757.
Agents Commonly Used in Combination
with Statins
 Bile acid sequestrants
 PPAR agonists (fibrates)
 Fish oils
 Niacin
 Ezetimibe
Role of Niacin in Combination Therapy

As monotherapy, niacin effects include:
 Increases in HDL-C
 Decreases in LDL-C, triglycerides, lipoprotein(a)
 Converts small LDL into more buoyant (less
atherogenic) particles

Safe and effective in combination with statins or
bile acid sequestrants
 Consider tolerability profiles of different
formulations
 May adversely effect glucose, insulin sensitivity
Miller M. Mayo Clin Proc. 2003;78:735.
Niaspan® Combination Therapy When
Response to Statin is Insufficient
Addition of Niaspan to Stable Dose of a Statin
Percent Change from baseline
31
30
23% 24%
20
10
0
-10
-20
-8%
-8%
-18%
-23%
-30
-24%
-30%
-40
TC
LDL
1g NIASPAN (n=66)
HDL
TG
2g NIASPAN (n=29)
Wolfe et.al. Am J Cardiol 2001; 87:476-489
Niacin in Combination with Statins

Stein et al—17-week randomized trial; N=180
 Immediate-release niacin plus simvastatin more
effective than either drug alone at raising HLD-C
and lowering VLDL-C

Guyton et al—48-week open-label trial; N=269
 ER niacin plus statin (lovastatin, pravastatin,
simvastatin):
 Reduced TC 23%; LDL-C 32%; TG 30%; Lp(a)
19%
 Increased HDL-C 26%
Stein et al. J Cardiovasc Pharmacol Ther. 1996;1:107.
Guyton et al. Am J Cardiol. 1998;82:737.
Enhanced Lipid-lowering with Combination Niacin
Extended-release Plus Lovastatin vs Statin Monotherapy
% Change from Baseline
Week 8
Week 12
Niacin ER+L
(1000/40 mg)
Atorvastatin (10
mg)
Niacin ER+L
(1000/40 mg)
Simvastatin
(20 mg)
LDL-C
–38%*
–38%*
–42%*
–35%
HDL-C
+20%*†
+3%
+19%*†
+8%
TG
–30%*†
–20%
–36%*†
–15%
Lp(a)
–16%*†
+8%
–20%*†
–1%
*P≤ 0.05 vs simvastatin; †P ≤ 0.05 vs atorvastatin
Bays H, et al. Am J Cardiol. 2003;91:667-672.
Issues of Safety and Tolerability
of Niacin and Fibrates



Niacin
 Chief complaint is flushing, intolerable in 10% of patients
 Also conjunctivitis, nasal stuffiness, loose stools/diarrhea,
acanthosis nigricans, ichthyosis, hepatitis
Fibrates
 Abdominal discomfort, possible gallstones
 Myositis with impaired renal function
Increased risk of rhabdomyolysis with fibrate or niacin + statin
Statin
Atorvastatin
Fluvastatin
Lovastatin
Pravastatin
Simvastatin
No. of Cases of Rhabdomyolysis Associated With:
Fibrates
Niacin
10
Not reported
4
Not reported
5
1
6
1
33
2
Knopp RH. N Engl J Med. 1999;341:498-511; Jones PH, Davidson MH. Am J Cardiol. 2005;95:120-122; Bellosta S, et al. Circulation. 2004;109(23 Suppl 1):III50-57
Agents Commonly Used in Combination
with Statins
 Bile acid sequestrants
 PPAR agonists (fibrates)
 Fish oils
 Niacin
 Ezetimibe
Increased biliary cholesterol secretion in
patients with obesity
(mg/day)
Absorption
Cholesterol secretion
1451 mg/day
Absorption
666 mg/day
Non-obese
Absorption rate
63%
Obese
59%
Ref; Mok, von Bergmann,Grundy, Journal of Lipid Research 20, 389, 1979
Increased cholesterol absorption in
diabetic patients with CHD
(%)
Cholesterol Absorption
35
(mg/kg/d)
25
Cholesterol Synthesis
NS
p<0.05
30
20
25
15
20
15
10
10
5
5
0
0
CHD (+)
CHD (-)
CHD (+)： n=7, Total chol: 6.01±0.33 (mmol)
CHD (+)
CHD (-)
CHD (-): n=6, Total chol: 6.25±0.27 (mmol)
Gylling H, Miettinen TA: Atherosclerosis 1996; 126: 325-332.
Ezetimibe Blocks Cholesterol Metabolism
at a New Site
Bile acid
sequestrants
Bile acids
X
Free cholesterol
Brush
Border
X
X
Sterols/
Micelles
Remnants
Statins
Unstirred
water
layer
Cholesterol
DIET
stanols
X
CE
Synthesis
Plaque
formation
ENTEROCYTE
BLOOD
FC biosynthesis
FC
X
ACAT
Cholesteryl
Ester (CE)
CE
Chylomicrons
Cholesterol Absorption Inhibitors (e.g., ezetimibe)
Ezetimibe: Indications
 Hypercholesterolemia
 Monotherapy
 Combination therapy with statins
 Homozygous familial
hypercholesterolemia
 Homozygous sitosterolemia
Note:
no data are yet available on effects of ezetimibe (alone or in
combination therapy) on CHD morbidity and mortality
Bays H. Expert Opin Investig Drugs. 2002;11:1587-1604.
Ezetimibe: Mechanism of Action
 Selective inhibition of intestinal cholesterol
absorption
•  Intestinal delivery of cholesterol to liver
•  Expression of hepatic LDL receptors
•  Cholesterol content of atherogenic particles
 Enterohepatic circulation of ezetimibe and
active glucuronide metabolite
• Delivers agent back to site of action
• Limits systemic exposure
Bays H. Expert Opin Investig Drugs. 2002;11:1587-1604.
Low Systemic Exposure of Ezetimibe May Reduce
Potential for Adverse Effects/ Drug Interactions
3H-DPM
(x 10–6)
3 h post-3H ezetimibe IV dosing
Intestinal
lumen
Intestinal
wall
Plasma
Liver
van Heek M, et al. Br J Pharmacol. 2000;129:1748-1754.
Bile
Ezetimibe: Dosage and Administration
 10 mg once daily
 Any time of day, with or without food
 May be taken concomitantly with statin
 Dosage adjustment not necessary according
to
 Gender
 Mild hepatic or renal insufficiency
 Age (ie, elderly)
 Ezetimibe not recommended in children <10 years old
Bays H. Expert Opin Investig Drugs. 2002;11:1587-1604.
Ezetimibe: Contraindications
 Hypersensitivity to any component of agent
 Combination with statins in patients with
active liver disease or unexplained
persistent elevations in serum
transaminases
 Pregnancy C category as monotherapy (no
adequate studies in pregnant women)
 All statins are contraindicated in pregnant and
nursing women
 Precaution: Moderate or severe hepatic
insufficiency
Bays H. Expert Opin Investig Drugs. 2002;11:1587-1604.
Ezetimibe “Add On” Study:
Improved Lipid Profiles
LDL-C
5
1.0
% Reduction from
Baseline at Week 8
0
-5
HDL-C
TG
2.7†
–2.9
–3.7
-10
-15
–14.0‡
-20
-25
Statin + Placebo (n=390)
–25.1*
-30
Statin + Ezetimibe 10 mg (n=379)
*P<0.001; †P<0.05; ‡P<0.001
.
Gagné C, et al. Am J Cardiol. 2002;90:1084-1091
LDL-C Reduction across the Dose Range
VYTORIN™ vs. Simvastatin Efficacy Study
10/20 mg
20 mg
10/40 mg
40 mg
10/80 mg
80 mg
(n=86)
(n=89)
(n=89)
(n=90)
(n=91)
(n=87)
Mean % change
from baseline to week 12
0
–10
–20
–30
–35%
–40
–50
–42%
–51%*
–46%
–55%*
–60
–61%*
–70
VYTORIN
Simvastatin
*p<0.001 vs. corresponding dose of simvastatin
Adapted from Goldberg AC et al Mayo Clin Proc 2004;79:620–629.
VYTORIN™ (ezetimibe/simvastatin) is a trademark of MSP Singapore Company, LLC.
Patients at NCEP Goal (%)
Ezetimibe “Add On” Study: Marked Increase
in Patients Reaching Treatment Goals
100
72% *
80
60
40
19%
20
0
Statin + Placebo
(n=390)
Statin + Ezetimibe
(n=379)
*P<0.001
Gagné C, et al. Am J Cardiol. 2002;90:1084-1091.
Effect of Ezetimibe on LDL-C in
Type 2 Diabetes Subgroup
Total Population
Diabetes Subgroup
% Change From Baseline
0
-5
-2
-4
-10
-15
-20
-25
-25*
-28*
-30
Statin and EZE (n=90)
* p<0.001 vs statin + placebo
Simons et al. EASD 2002
Statin and PBO (n=98)
Changes in Other Cardiovascular
Parameters
Apo B
(n=340)
(n=328)
Non–HDL-C
(n=353)
(n=345)
CRP
(n=209)
(n=204)
Mean* % change
from baseline to week 12
0
–9%
–20
–29%
–34%
–40
–33%**
–42%**
–60
–49%**
Eze/Simva 10/10–10/80 mg pooled doses
Simvastatin 10–80 mg pooled doses
*Except for CRP, shown as median percent changes
**p<0.001 vs. simvastatin 10–80 mg
Statin and Complementary GI-Acting Drugs
vs Statin Titration
6%
Statin at starting dose
6%
1st
6%
2nd
3rd
3-STEP
TITRATION
Doubling
18%
Statin at starting dose
+ GI-acting
drug
% Reduction in LDL-C
Bays H, et al. Expert Opin Pharmacother. 2003;4:779-790.
1-STEP
COADMINISTRATION
VYTAL Study
Optional LDL-C Goal to <1.8 mmol/L (<70 mg/dL)
in Diabetes Patients: Ezetimibe/Simvastatin Superior to Atorvastatin
P<0.001
P<0.001
Patients With LDL-C
<1.8 mmol/L at Week 6, %
80
70
74.4
59.7 P<0.001
55.2
60
50
40
35
30
21.5
20
10
0
Ezetimibe/
Simvastatin
10/20 mg
(n=238)
Atorvastatin
10 mg
(n=237)
Usual Starting Doses
Atorvastatin
20 mg
(n=240)
Ezetimibe/
Simvastatin
10/40 mg
(n=242)
Atorvastatin
40 mg
(n=241)
Next-Higher Doses
Adapted from Goldberg RB, et al. Mayo Clin Proc. 2006;81:1579–1588.
52
Large Clinical Outcomes Program in
>21,000 Patients at High-Risk of CV Events
Study, N
Study Population
Treatments
Primary
Endpoint
ENHANCE,
~725
HeFH
Ezetimibe/
simvastatin 10/80 mg
Simvastatin 80 mg
CA IMT
SHARP,
~9000
Chronic kidney disease
Ezetimibe/
simvastatin 10/20 mg
Placebo
CV outcomes (MI,
stroke, coronary
revascularization)
SEAS,
~1400
Asymptomatic aortic
stenosis with LDL-C
<6 mmol/L
Ezetimibe/
simvastatin 10/40 mg
Placebo
CV death, aortic
surgery, CV
outcomes
Ezetimibe/
simvastatin 10/40 mg
Simvastatin 40 mg
CV death, major
coronary events,
stroke
IMPROVE-IT, ACS
~10,000
CA IMT = Carotid artery intima-media thickness
Adapted from Kastelein JJP, et al. Am Heart J. 2005;149:234–239; Baigent C, Landry M. Kidney Int. 2003;63(suppl 84):S207–S210; Oxford Clinical Trial Service Unit. The
Study of Heart and Renal Protection (SHARP). Available at: http://www.ctsu.ox.ac.uk/ ~sharp/. Accessed June 2005; Rossebo A, et al, for the SEAS Steering
Committee. Presented at: XIII International Symposium on Atherosclerosis; September 23–October 2, 2003; Kyoto, Japan. Poster 3P-0870; Schering-Plough.
IMPROVE-IT: Examining outcomes in subjects with acute coronary syndrome: Vytorin (ezetimibe/simvastatin) vs simvastatin (Study P04103). Available at:
http://www.clinicaltrials.gov/ct/show/NCT00202878. Accessed November 2006.
T Killilea et al Am J Managed Care Vol 12, No. 11 Sup. Pps S 325-332
54
Conclusion:
 Different lipid-lowering agents affect
different lipid parameters
 Combination therapy may further reduce
CHD risk vs monotherapy
 Consider combination therapy if:
 Treatment goals cannot be met with statins alone
 Risk for intolerance, toxicity, or adverse drug
interactions with higher dose of single lipidlowering agent
55
Conclusions
 Inhibition of cholesterol absorption and
production via coadministration of ezetimibe
with a statin or ezetimibe/simvastatin in the
single tablet
 Is helping to set a new standard
 Provides greater efficacy than statin therapy
alone to get patients to a lower LDL-C goal
 Outcomes studies will determine if the risk of
cardiac endpoints decreases as LDL-C levels
decrease with ezetimibe/simvastatin
Treatment Paradigm
Combination therapy-Statin plus what?
For LDL


Cholesterol absorption inhibitor –
Ezetimibe/Ezetrol®

Bile acid sequestrant
For HDL


Niacin/Niaspan®/Fibrate
For TG


Fibrate (fenofibrate)/Niacin/Niaspan®
Thank you
58
Statin Evidence/Cost/Efficacy Grid
©
Continuing Medical Implementation ®
STATIN
Lovastatin
(generic)
Pravastatin
(generic)
Simvastatin
(generic)
Fluvastatin
(generic)
Atorvastatin
Rosuvastatin
Dose Cost/tab $ %LDL Red %LDL Red %LDL Red
Law[7]
Stellar[8]
[1]
20mg
40mg
10mg
20mg
40mg
5mg
10mg
20mg
40mg
80mg
20mg
40mg
XL 80mg
10mg
20mg
40mg
80mg
5 mg
10mg
20mg
40mg
Revised January 2007
1.30
2.40
1.05
1.25
1.50
0.45
0.89
1.10
1.10
1.10
0.75
1.05
1.30
1.66
2.08
2.24
2.24
1.29
1.36
1.70
1.99
26
31
22
25
30
27
30
35
40
46[2]
19
29
36
40[3]
45
51
58[4]
42[5]
52
55
63[6]
29
37
20
24
29
23
27
32
37
42
21
27
33
37
43
49
55
38
43
48
53
30%
35%
%LDL Reduction
40%
45%
50%
55%
2.4
20
24
30
28
35
39
46
1.5
0.89
1.10
1.10
1.10
1.05
1.30
37
43
48
51
1.66
2.08
2.24
2.24
1.29
46
52
55
1.36
1.70
1.99
*
* Average % reduction: Use to estimate initial statin dose. Actual response varies by patient and subgroup (age and gender).
Cost based on Ontario ODB pricing-updated February 2003. For cost to patient, add 10% plus prescribing fee.
Evidence
Cost
HPS/ASCOT/CARDS
Select Statin based on efficacy, safety, evidence and cost.
© Continuing Medical Implementation ®
REVERSAL
PROVE-IT/TNT/IDEAL/AtoZ/SPARCL
ASTEROID
© Continuing
Medical Implementation
®
…...bridging theJ Card
care1998;81:
gap 582-587
[1]Ann Intern Med.
1996;125:990-1000.[2]Am
J Card;1998:82:311-316.[3]Arterioscler
Thromb Vasc Biol. 1995;15:678-682.[4]Am
[5] Am J Cardiol 2003;91:33–41 [6]EHJ 2002, 4, (August) Abstract Supplement: Abs 212, page 19.[7]BMJ 326 974040:1423.[8]JACC 2003 (suppl):315A-316A. Abs 876-2.
60%
59
Statin Evidence/Cost/Efficacy Grid
©
Continuing Medical Implementation ®
STATIN
Lovastatin
(generic)
Pravastatin
(generic)
Simvastatin
(generic)
Fluvastatin
(generic)
Atorvastatin
Rosuvastatin
Dose Cost/tab $ %LDL Red
20mg
40mg
10mg
20mg
40mg
5mg
10mg
20mg
40mg
80mg
20mg
40mg
XL 80mg
10mg
20mg
40mg
80mg
5 mg
10mg
20mg
40mg
Revised January 2007
1.30
2.40
1.05
1.25
1.50
0.45
0.89
1.10
1.10
1.10
0.75
1.05
1.30
1.66
2.08
2.24
2.24
1.29
1.36
1.70
1.99
[1]
%LDL Red
Law[7]
26
31
22
25
30
27
30
35
40
46[2]
19
29
36
40[3]
45
51
58[4]
42[5]
52
55
63[6]
29
37
20
24
29
23
27
32
37
42
21
27
33
37
43
49
55
38
43
48
53
%LDL Red
Stellar[8]
30%
35%
%LDL Reduction
40%
45%
50%
55%
60%
2.4
20
24
30
28
35
39
46
1.5
0.89
1.10
1.10
1.10
1.05
1.30
37
43
48
51
1.66
2.08
2.24
2.24
1.29
46
52
55
1.36
1.70
1.99
*
* Average % reduction: Use to estimate initial statin dose. Actual response varies by patient and subgroup (age and gender).
Cost based on Ontario ODB pricing-updated February 2003. For cost to patient, add 10% plus prescribing fee.
Evidence
Cost
HPS/ASCOT/CARDS
Select Statin based on efficacy, safety, evidence and cost.
© Continuing Medical Implementation ®
REVERSAL
PROVE-IT/TNT/IDEAL/AtoZ/SPARCL
ASTEROID
© Continuing
Medical Implementation
®
…...bridging the Jcare
gap 582-587
[1]Ann Intern Med.
1996;125:990-1000.[2]Am
J Card;1998:82:311-316.[3]Arterioscler
Thromb Vasc Biol. 1995;15:678-682.[4]Am
Card 1998;81:
[5] Am J Cardiol 2003;91:33–41 [6]EHJ 2002, 4, (August) Abstract Supplement: Abs 212, page 19.[7]BMJ 326 974040:1423.[8]JACC 2003 (suppl):315A-316A. Abs 876-2.
60
STATIN
Statin/Combination Therapy
Cost Efficacy
Lovastatin
(generic)
Pravastatin
(generic)
Simvastatin
(generic)
Fluvastatin
(generic)
Atorvastatin
Rosuvastatin
Ezetimibe
Dose
20mg
40mg
10mg
20mg
40mg
5mg
10mg
20mg
40mg
80mg
20mg
40mg
XL 80mg
10mg
20mg
40mg
80mg
5 mg
10mg
20mg
40mg
10mg
Cost/tab % LDL Red % LDL Red % LDL Red
Law [7]*
Stellar [8]
$
[1]
1.30
2.40
1.05
1.25
1.50
0.45
0.89
1.10
1.10
1.10
0.75
1.05
1.30
1.66
2.08
2.24
2.24
1.29
1.36
1.70
1.99
1.63
26
31
22
25
30
27
30
35
40
46[2]
19
29
36
40[3]
45
51
58[4]
42[5]
52
55
63[6]
18[9]
Cost ($) for
30%
35%
% LDL reduction on mono or combination therapy
40%
45%
50%
55%
60%
65%
29
37
2.4
20
20
24
24
29
30
1.5
23
27
28
0.89
2.52
32
35
1.10
2.73
37
39
1.10
42
46
1.10
21
27
1.05
33
1.30
37
37
1.66
43
43
2.08
49
48
55
51
38
1.29
43
46
1.36
48
52
53
55
(Co-administration with statin yields incremental 21-25% LDL reduction)
2.73
2.73
3.29
3.71
2.24
3.87
2.24
3.87
2.99
1.70
* Average % reduction: Use to estimate initial statin dose. Actual response varies by patient and subgroup (age and gender).
Cost based on Ontario ODB pricing-updated February 2003. For cost to patient, add 10% plus prescribing fee.
Select Statin based on efficacy, safety, evidence and cost.
Evidence
Cost
HPS/ASCOT/CARDS
70%
1.99
3.62
Select combination therapy
with ezetimibe 10 mg to achieve
greater LDL reduction
With ezetimibe 10 mg - $ > statin
monotherapy or alternate statin
REVERSAL
PROVE-IT/TNT/IDEAL/AtoZ/SPARCL
ASTEROID
[1]Ann Intern Med. 1996;125:990-1000.[2]Am J Card;1998:82:311-316.[3]Arterioscler Thromb Vasc Biol. 1995;15:678-682.[4]Am J Card 1998;81: 582-587
[5] Am J Cardiol 2003;91:33–41 [6]EHJ 2002, 4, (August) Abstract Supplement: Abs 212, page 19.[7]BMJ 326 974040:1423.[8]JACC 2003 (suppl):315A-316A. Abs 876-2.
©al.Continuing
Medical
Implementation
…...bridging the care gap
[9] Dujovne CA et
Am J Cardiol 2002;
90. (10):1092-7.Knopp
RH et al. Eur®
Heart J 2003;24:729-41
Revised January 2007
© Continuing Medical Implementation ®