Doubletree Hotel Seattle Airport

1
2008
Symposia Series 2

• Doubletree Hotel Seattle Airport
• Seattle, Washington
• June 21, 2008

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2
DyslipidemiaWhen Statins Alone Fail

• Joyce L. Ross, MSN, ANP, CRNP, CS
• Certified Clinical Lipid Specialist
• Diplomat, Accreditation Council for Clinical
  Lipidology
• Cardiovascular Risk Intervention Program
• University of Pennsylvania
• Philadelphia, Pennsylvania

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Faculty Disclosure

• Ms Ross consultant Kaneka America LLC speakers
  bureau Abbott Laboratories, AstraZeneca
  International, Bristol-Myers Squibb, Pfizer Inc

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4
What percentage of your patients with
dyslipidemia who are receiving statin therapy
alone achieve their LDL-C goal?
?
KEY QUESTION

• 25
• 26-50
• 51-75
• 76-100

Use your keypad to vote now!
LDL-C low-density lipoprotein cholesterol.
5
For what percentage of your patients do you use
nonHDL-C to guide management of dyslipidemia?
?
KEY QUESTION

• 25
• 26-50
• 51-75
• 76-100

Use your keypad to vote now!
HDL-C high-density lipoprotein cholesterol.
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Learning Objectives

• Identify patients who would benefit from
  combination therapy for dyslipidemia based on
  results of recent clinical trials
• Develop optimal treatment strategies for lowering
  LDL-C and raising HDL-C levels in patients with
  mixed dyslipidemia
• Educate patients on the benefits and long-term
  safety data associated with combination drug
  therapy for dyslipidemia

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Case Study
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History and Physical Findings

• 68-year-old white woman
• History
• Type 2 diabetes mellitus (10 years)
• Hypertension (12 years)
• Stage 3 renal insufficiency (3 years)
• Physical findings
• Height 5 ft 3 in weight 185 lb waist
  circumference 39 in BMI 32.8 kg/m2
• BP 126/72 mm Hg
• ABI 0.84

ABI ankle-brachial index BMI body mass
index BP blood pressure.
9
Current Medications

• Lisinopril/hydrochlorothiazide (20/12.5 mg once
  daily)
• Pravastatin (80 mg once daily)
• Glimepiride (2 mg once daily)
• Metformin (850 mg twice daily)
• Acetylsalicylic acid (aspirin) 81 mg (once daily)

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Laboratory Results

• Lipid profile
• TC 178 mg/dL
• LDL-C 72 mg/dL
• HDL-C 44 mg/dL
• TG 240 mg/dL
• NonHDL-C 134 mg/dL
• Glucose metabolism
• FPG level 114 mg/dL
• A1C 6.9

• Renal function
• Creatinine 1.3 mg/dL
• Estimated GFR 54 mL/min
• Microalbumin 34 mg/L

A1C glycosylated hemoglobin FPG fasting
plasma glucose GFR glomerular filtration rate
TC total cholesterol TG triglyceride.
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What is this patients CHD risk category?
?
DECISION POINT

• Very high
• High
• Moderately high
• Moderate
• Low

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CHD coronary heart disease.
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Type 2 Diabetes and CHD 7-Year Incidence of
Fatal/Nonfatal MI (East West Study)
Patients without diabetes Patients with
diabetes (n 1373) (n 1059)
MI myocardial infarction. At baseline. Haffner
SM, et al. N Engl J Med. 1998339229-234.
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NCEP ATP III 2004 Update Risk Categories
CVD cardiovascular disease NCEP ATP III
National Cholesterol Education Program Adult
Treatment Panel III. Adapted from Grundy SM, et
al. Circulation. 2004110227-239.
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What would be your next step in treating this
patient?
?
DECISION POINT

• Change pravastatin (80 mg once daily) to
  atorvastatin (80 mg once daily)
• Add pioglitazone (15 mg once daily) to her
  pravastatin regimen
• Add fenofibrate (145 mg/d) to her pravastatin
  regimen
• Add omega-3 fatty acids to her pravastatin
  regimen
• Add niacin to her pravastatin regimen and titrate
  slowly to effective dose

Use your keypad to vote now!
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15
Treatment Decision (Option 1)

• What would be your next step in treating this
  patient?
• Change pravastatin (80 mg once daily) to
  atorvastatin (80 mg once daily)
• Add pioglitazone (15 mg once daily) to her
  pravastatin regimen
• Add fenofibrate (145 mg/d) to her pravastatin
  regimen
• Add omega-3 fatty acids to her pravastatin
  regimen
• Add niacin to her pravastatin regimen and titrate
  slowly to effective dose

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Residual CHD Risk in Major Statin Trials
CHD events occur in patients treated with statins
Placebo
Statin
28.0
Patients Experiencing Major CHD Events ()
19.4
15.9
13.2
11.8
12.3
10.2
10.9
7.9
8.7
6.8
5.5
4S1
LIPID2
CARE3
HPS4
WOSCOPS5
AFCAPS/ TexCAPS6
N
4444
4159
20,536
6595
6605
9014
? LDL
-35
-28
-29
-26
-25
-25
Secondary
High Risk
Primary
1. 4S Group. Lancet. 19943441383-1389 2. LIPID
Study Group. N Engl J Med. 19983391349-1357 3.
Sacks FM, et al. N Engl J Med. 19963351001-1009
4. HPS Collaborative Group. Lancet.
20023607-22 5. Shepherd J, et al. N Engl J
Med. 19953331301-1307 6. Downs JR, et al.
JAMA. 19982791615-1622.
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Patients With Diabetes Have Particularly High
Residual CVD Risk After Statin Treatment
CHD death, nonfatal MI, stroke,
revascularizations CHD death, nonfatal MI, CABG,
PTCA CHD death and nonfatal MI CHD death,
nonfatal MI, stroke CHD death, nonfatal MI,
resuscitated cardiac arrest, stroke (80-mg vs
10-mg atorvastatin)
MI myocardial infarction PTCA percutaneous
transluminal coronary angioplasty.
1. HPS Collaborative Group. Lancet.
20033612005-2016. 2. Sacks FM, et al. N Engl J
Med. 19963351001-1009. 3. LIPID Study Group. N
Engl J Med. 19983391349-1357.4. Shepherd J, et
al. Lancet. 20023601623-1630. 5. Sever PS, et
al. Lancet. 20033611149-1158. 6. Shepherd J, et
al. Diabetes Care. 2006291220-1226.
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Independent risk factors for CVD in patients
with diabetes and the metabolic syndrome include
?
KEY QUESTION

• Low TG levels and high LDL-C levels
• Low TG levels and high HDL-C levels
• High TG levels and low LDL-C levels
• High TG levels and low HDL-C levels

Use your keypad to vote now!
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Atherogenic Dyslipidemia in Patients With
Diabetes and the Metabolic Syndrome

• High TG levels (independent CVD risk factor)
• TG-rich remnant lipoproteins (VLDL)
• Altered metabolism (lipolysis) of LDL and HDL
  particles
• Absolute levels of LDL-C are commonly not
  significantly increased, but other LDL parameters
  significantly change
• ? Number of LDL particles (? LDL-P and Apo B)
• Predominantly small, dense LDL-P
• Low levels of HDL-C (major independent CVD risk
  factor)
• May reduce reverse cholesterol transport

Apo B apolipoprotein B LDL-P LDL particle
VLDL very low-density lipoprotein. Garvey WT,
et al. Diabetes. 200352453-462 Haffner SM.
Diabetes Care. 200326 (suppl 1)S83-S86.
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Atherogenic Changes Associated With High TG
Levels
Low HDL-C
Increased VLDL Remnants
Small, Dense LDL-P
HYPERTRIGLYCERIDEMIA
Coagulation Changes Increased PAI-1 Increased
fibrinogen
Increased Chylomicron Remnants
PAI-1 plasminogen activator inhibitor type
1. Source Vascular Biology Working Group.
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Risk of CHD by TG LevelThe Framingham Heart
Study
Castelli WP. Am J Cardiol. 1992703H-9H.
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Risk of CHD by TG LevelPROCAM Study
8-Year Follow-Up
N 4639 men with no history of MI or stroke

• Elevated TG levels significantly increase CHD
  risk
• Significant correlation remains between TG level
  and CHD risk after adjustment for LDL-C and HDL-C
  
• 6-fold increased CHD risk in patients with TG
  gt200 mg/dL and LDL-CHDL-C gt5

P .001
2.6
P .01
1.6
Comparator 1.0
Relative CHD Risk
Assmann G, et al. Am J Cardiol.
1996771179-1184.
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TG Level Is Significant CVD Risk Factor Recent
Meta-Analysis of 29 Studies
Groups CHD Cases
N 262,525
Duration of follow-up
10 years 5902
lt10 years 4256
Sex
Male 7728
Female 1994
Fasting status
Fasting 7484
Nonfasting 2674
Adjusted for HDL
Yes 4469
No 5689
1.72 (1.56-1.90)
Individuals in top vs bottom third of usual
log-TG values adjusted for at least age, sex,
smoking status, and lipid concentrations also
adjusted for BP (in most studies).
2
1
CHD Risk Ratio (95 CI)
Sarwar N, et al. Circulation. 2007115450-458.
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NCEP ATP III TG-Rich Remnant Lipoproteins Are
Atherogenic

• Elevated TG levels are a marker for elevated
  levels of atherogenic remnant lipoproteins
• VLDL-C is the most readily available measure of
  atherogenic remnant lipoproteins for clinical
  practice
• When TG levels are elevated, nonHDL-C better
  represents the concentrations of all atherogenic
  lipoproteins than LDL-C alone
• NonHDL-C is a secondary target of therapy when
  TG levels are 200 mg/dL as defined by the NCEP

VLDL-C very low-density lipoprotein
cholesterol. NCEP ATP III. Circulation.
20021063143-3421.
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Importance of NonHDL-C

• Calculate nonHDL-C when
• TGs are ?200 mg/dL
• Target goal is ?30 mg/dL higher than LDL-C goal
• Example
• TG 240 mg/dL gt200 need nonHDL-C
• TC 178 mg/dL 178
• HDL-C 44 mg/dL - 44
• LDL-C 72
• NonHDL-C 134 mg/dL
• Patients LDL-C goal ?70 nonHDL-C goal ?100
  mg/dL

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In patients with diabetes who receive statin
therapy to reduce LDL-C levels
?
KEY QUESTION

• Residual CVD risk remains high
• Residual CVD risk is low
• Residual CVD risk has no impact on event rates
• Residual CVD risk from low HDL-C levels is not
  clinically significant

Use your keypad to vote now!
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Key Points

• Residual CVD risk remains after patients are
  treated with statins to reduce LDL-C and is
  particularly high in patients with diabetes who
  are treated with statins
• Atherogenic dyslipidemia contributes to residual
  risk for atherosclerosis and CVD risk
• Increased levels of TG and TG-rich remnant
  lipoproteins
• Increased levels of nonHDL-C
• Increased numbers of Apo Bcontaining particles,
  including small, dense LDL
• Decreased levels of HDL-C
• The combination of high TG with low HDL-C and/or
  high LDL-C synergistically increases CHD risk

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Treatment Decision (Option 2)

• What would be your next step in treating
• this patient?
• Change pravastatin (80 mg once daily) to
  atorvastatin (80 mg once daily)
• Add pioglitazone (15 mg once daily) to her
  pravastatin regimen
• Add fenofibrate (145 mg/d) to her pravastatin
  regimen
• Add omega-3 fatty acids to her pravastatin
  regimen
• Add niacin to her pravastatin regimen and titrate
  slowly to effective dose

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PROACTIVE Primary End Point
Placebo No. of events
572 Pioglitazone No. of events 514
25
20
N 5238
15
Proportion of Events ()
10
HR 0.90 (95 CI, 0.80-1.02) P .095
5
0
6
12
18
24
30
36
0
Time From Randomization (mo)
Death from any cause, nonfatal MI (including
silent MI), stroke, acute coronary syndrome, leg
amputation, coronary revascularization, or
revascularization of the leg. HR hazard
ratio. Dormandy JA, et al. Lancet.
20053661279-1289.
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PROACTIVE Secondary End Point
Placebo No. of events
358 Pioglitazone No. of events 301
25
20
N 5238
15
Proportion of Events ()
10
HR 0.84 (95 CI, 0.72-0.98) P .027
5
0
6
12
18
24
30
36
0
Time From Randomization (mo)
Death from any cause, nonfatal MI (excluding
silent MI), or stroke. Dormandy JA, et al.
Lancet. 20053661279-1289.
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Treatment Decision (Option 3)

• What would be your next step in treating
• this patient?
• Change pravastatin (80 mg once daily) to
  atorvastatin (80 mg once daily)
• Add pioglitazone (15 mg once daily) to her
  pravastatin regimen
• Add fenofibrate (145 mg/d) to her pravastatin
  regimen
• Add omega-3 fatty acids to her pravastatin
  regimen
• Add niacin to her pravastatin regimen and titrate
  slowly to effective dose

32
Treatment Decision (Option 3) 3-Month Follow-up

• Visit 1
• TLC (diet, exercise) reinforced
• Fenofibrate (145 mg/d) prescribed as add-on to
  her statin therapy
• Visit 2
• Improvements in lipid profile
• No musculoskeletal side effects no hepatic or
  renal laboratory abnormalities

33
Treatment Decision (Option 3) 3-Month
Follow-up (contd)

• After 3 months therapy with pravastatin plus
  fenofibrate

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Treating Beyond LDL-C Other Targets of
Lipid-Lowering Therapy

• Lipoproteins other than LDL are involved in
  atherogenesis (pro VLDL, IDL anti HDL)1
• NCEP ATP III concluded (on the basis of several
  types of data) that an elevated nonHDL-C in
  patients with hypertriglyceridemia will impart
  increased risk even after the goal of LDL-C has
  been reached1
• NCEP ATP III 2004 update For those high-risk
  patients who have elevated triglycerides or low
  HDL-C levels, addition of a fibrate or nicotinic
  acid to LDL-lowering therapy can be considered.2

IDL intermediate-density lipoprotein.
1. Grundy SM. Circulation. 20021062526-2529 2.
Grundy SM, et al. Circulation. 2004110227-239.
35
Outcomes in Fibrate Trials Patients With
Diabetes or Metabolic Syndrome
Major CVD Event Rate
P
Control
RRR
Drug
N
Trial
Primary Prevention
lt.005
13.0
71
3.9
292
HHS1
.004
19
8.9
10.8
7664
FIELD2
Secondary Prevention
.03
18.4
25
14.1
1470
BIP3
.004
29.4
32
21.2
769
VA-HIT4
Patients with TG gt204 mg/dL and an LDLHDL gt5
(may or may not have had diabetes or metabolic
syndrome). Patients with diabetes and no prior
CVD. Patients with metabolic syndrome. Patients
with diabetes.
1. Manninen V, et al. Circulation. 19928537-45
2. Keech A, et al. Lancet. 20053661849-1861 3.
Tenenbaum A, et al. Arch Intern Med.
20051651154-1160 4. Rubins HB, et al. Arch
Intern Med. 20021622597-2604.
36
VA-HIT CVD Risk Reduction in Diabetics Compared
With Nondiabetics
Combined End Point
Nonfatal MI
CHD Death
Stroke
0
5
3
P .88
10
10
15
P .67
Cumulative Event Rate Change ()
20
18
22
21
P .07
25
P .09
P .17
30
32
35
P .004
DM
40
No DM
40
41
P .26
45
P .046
P .02
DM diabetes mellitus. Rubins HB, et al. Arch
Intern Med. 20021622597-2604.
37
FIELD Primary and Secondary End Points
11 Reduction P .035
Placebo
Fenofibrate
21 Reduction P .003
11 Reduction P .16
24 Reduction P .01
Event Rate ()
19 Increase P .22
Total CVD Events (Secondary End Point)
CHD Death
Nonfatal MI
CHD Events (Primary End Point)
Coronary Revascularization
Nonfatal MI and CHD death. CHD events, stroke,
CVD death, revascularizations.
Keech A, et al. Lancet. 20053661849-1861.
38
FIELD End Points in Patients With No Prior CVD
(78 of Study Population)
CHD Events
Total CVD
(n 7664)
(n 7664)
0
-5
-10
Risk Reduction ()
-15
-20
-19
P .004
-25
Secondary End Point
-25
P .014
-30
Primary End Point
Keech A, et al. Lancet. 20053661849-1861.
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Fibrate/statin combination therapy has the
potential to increase the risk of
?
KEY QUESTION

• Arrhythmia
• Myopathy
• Osteoporosis
• Thrombosis

Use your keypad to vote now!
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Safety of Fibrate/Statin Combination Therapy

• Fibrates improve all components of atherogenic
  dyslipidemia and appear to reduce the risk for
  CVD their use in combination with statins is
  particularly attractive1
• Both statins and fibrates have the potential to
  produce myopathy, and the risk for myopathy is
  enhanced when they are used together1
• Clinical and preclinical studies indicate that
  gemfibrozil interferes with catabolism of statins
  in the liver (ie, inhibits glucuronidation),
  which can raise statin blood levels, thereby
  predisposing to myopathy1-3
• Fenofibrate does not interact adversely with
  statin catabolism and thus may be safer to use in
  combination therapy with statins1-3

1. Grundy SM, et al. Circulation.
2004109551-556 2. Davidson MH. Expert Opin
Drug Saf. 20065145-156 3. Davidson MH. Am J
Cardiol. 20029050K-60K.
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Number of Cases of Rhabdomyolysis in Combination
Therapy With Statins
10
8.6
9
8
7
6
No. Cases Reported per Million Prescriptions
5
15-Fold Increase
4
3
2
0.58
1
0
Fenofibrate
Gemfibrozil
Excludes cases involving cerivastatin.
Jones PH, et al. Am J Cardiol. 200595120-122.
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42
Treatment Decision (Option 4)

• What would be your next step in treating this
  patient?
• Change pravastatin (80 mg once daily) to
  atorvastatin (80 mg once daily)
• Add pioglitazone (15 mg once daily) to her
  pravastatin regimen
• Add fenofibrate (145 mg/d) to her pravastatin
  regimen
• Add omega-3 fatty acids to her pravastatin
  regimen
• Add niacin to her pravastatin regimen and titrate
  slowly to effective dose

43
Treatment Decision (Option 4)

• Data suggest omega-3 fatty acid supplementation
  is a useful treatment option for patients with
  hypertriglyceridemia
• This patients TG level (on statin monotherapy)
  is 240 mg/dL
• Interesting data available for omega-3 fatty
  acids include
• JELIS trial1
• GISSI-P trial2

1. Yokoyama M, et al. Lancet 20073691090-1098
2. GISSI-P Investigators. Lancet.
1999354447-455.
44
JELIS Omega-3 Fatty Acids Plus Statins in
Patients With Hypercholesterolemia

• All patients had TC levels gt6.5 mmol/L (gt251
  mg/dL)
• Randomized to treatment with a statin or a statin
  plus 1800 mg/d EPA

P .011
CABG coronary artery bypass graft EPA
eicosapentaenoic acid. Yokoyama M, et al. Lancet
20073691090-1098.
45
Dietary Supplementation With Omega-3 Fatty Acids
After MI
GISSI-P Results
Placebo (n 2828)
Omega-3 fatty acids 1 g (n 2836)
15 Reduction P .023
20 Reduction P .008
Event Rate ()
Death/ Nonfatal MI/ Nonfatal Stroke
CVD Death/ Nonfatal MI/ Nonfatal Stroke
GISSI-P Investigators. Lancet. 1999354447-455.
46
Efficacy of Omega-3 Fatty Acids for Patients
With Severe Hypertriglyceridemia
Placebo

Omega-3 fatty acids 4 g

Change From Baseline ()


TG level 500-2000 mg/dL, N 42. P lt.02 vs
placebo.
Harris WS, et al. J Cardiovasc Risk.
19974385-391.
47
Omega-3 Fatty Acids/Statin Combination Therapy in
Insulin-Resistant Obese Men
Atorvastatin 40 mg

Omega-3 fatty acids 4 g
Combination
Change From Baseline ()







LDL-C
NonHDL-C
HDL-C
TG
Insulin Resistance (HOMA Score)
N 48 P lt.05 vs placebo. HOMA homeostasis
model assessment.
Chan DC, et al. Diabetes. 2002512377-2386.
48
Treatment Decision (Option 5)

• What would be your next step in treating this
  patient?
• Change pravastatin (80 mg once daily) to
  atorvastatin (80 mg once daily)
• Add pioglitazone (15 mg once daily) to her
  pravastatin regimen
• Add fenofibrate (145 mg/d) to her pravastatin
  regimen
• Add omega-3 fatty acids to her pravastatin
  regimen
• Add niacin to her pravastatin regimen and titrate
  slowly to effective dose

49
Treatment Decision (Option 5)3-Month
Follow-up

• Visit 1
• TLC (diet, exercise) reinforced
• Long-acting niacin prescribed as add-on to statin
  therapy, at 500 mg/d and increased to 1000 mg/d
  after 4 weeks
• Visit 2
• Lipid profile improved
• No worsening of diabetes control noted
• Normal liver function studies

50
Treatment Decision (Option 5)3-Month Follow-up
(contd)

• After 3 months therapy with pravastatin plus
  niacin

51
NCEP ATP III HDL-C Is an Independent Risk Factor
for CHD

• A low HDL-C level is strongly and inversely
  associated with CHD risk
• Independent relationship holds after correction
  for other risk variables in multivariate
  analysis
• A low HDL-C level often correlates with
  elevations of serum TG and remnant lipoproteins
• HDL may be antiatherogenic
• Promotes reverse cholesterol transport
• Antioxidant and anti-inflammatory properties
  inhibit atherogenesis

NCEP ATP III. Circulation. 20021063143-3421.
51
52
Other Antiatherogenic Actions of HDL
Anti-inflammatory Activity
Reverse Cholesterol Transport CellularCholesterol
Efflux
HDL
Antiapoptotic Activity
Antithrombotic Activity
Antioxidative Activity
Anti-infectious Activity
VasodilatoryActivity
EndothelialRepair
Chapman MJ, et al. Curr Med Res Opin.
2004201253-1268. Assmann G, et al. Ann Rev Med.
200353321-341.
53
Meta-Analysis Predictive Value of HDL-C

• Coronary Primary Prevention Trial (CPPT)
• Multiple Risk Factor Intervention Trial (MRFIT)
• Lipid Research Clinics Prevalence Mortality
  Follow-up Study (LRCS)
• Framingham Heart Study (FHS)

1 mg/dL Increase in HDL-C
CPPT
MRFIT
LRCS
LRCS
FHS
FHS
2 ? CHD Risk in Men
3 ? CHD Risk in Women
Gordon DJ, et al. Circulation. 1989798-15.
53
54
Low HDL-C Increases CVD Risk Even If LDL-C
Levels Are Well ControlledTNT Study
Patients with LDL-C lt70 mg/dL (n 2661)
Hazard Ratio (95 CI) versus Q1 Q2 0.85
(0.57-1.25) Q3 0.57 (0.36-0.88) Q4 0.55 (0.35
-0.86) Q5 0.61 (0.38-0.97)
10
9
8
7
6
5-Year Risk of Major CV Events ()
5
4
3
2
1
0
Q1(lt37)
Q2(37 to lt42)
Q3(42 to lt47)
Q4(47 to lt55)
Q5(?55)
Quintile of HDL-C (mg/dL)
On-treatment level (3 months). Barter P, et al.
N Engl J Med. 20073571301-1310.
54
55
Lipid Effects of Adding Niacin ER to Baseline
Statin Therapy
Statin niacin ER 1 g (n 66)
Statin niacin ER 2 g (n 29)
Change From Baseline Statin Therapy ()
TG
TC
LDL-C
HDL-C
niacin ER niacin extended-release. Wolfe ML, et
al. Am J Cardiol. 200187476-479.
56
HATS Lipid-Altering/Antioxidant Therapy in
Patients With CAD and Low HDL-C

• S-N group mean LDL-C ? (-46), mean HDL-C ?
  (26)
• Placebo and AVit groups mean LDL-C and HDL-C
  levels unaltered
• Antioxidants ? HDL2 (protective component of HDL)
  levels and attenuated protective ? seen with S-N

Mean Change in Proximal Stenosis ()
Composite CV Event Rate ()
Composite of death from CV causes, nonfatal
infarction, or revascularization procedure. AVit
antioxidant vitamins CAD coronary artery
disease S-N simvastatin plus niacin. Brown BG,
et al. N Engl J Med. 20013451583-1592.
57
COMPELL Lipid Effects of Niacin ER/Statin
Combination Therapy
Atorvastatin 40 mg niacin ER 2 g
Simvastatin 40 mg ezetimibe 10 mg
Rosuvastatin 40 mg
Rosuvastatin 20 mg niacin ER 1 g




Change From Baseline ()


TG
LDL-C
HDL-C
Lp(a)
N 292 12 weeks. P lt.05 vs atorvastatin
niacin ER.
Lp(a) lipoprotein (a). McKenney JM, et al.
Atherosclerosis. 2007192432-437.
58
ADA Standards of Medical Care in
DiabetesDyslipidemia Management
An LDL-C goal lt70 mg/dL is an option in patients
with overt CVD. An HDL-C goal gt50 mg/dL should
be considered for women. At high doses, niacin
may increase blood glucose levels.
American Diabetes Association. Diabetes Care.
200427S68-S71. American Diabetes Association.
Diabetes Care. 200730(suppl 1)S4-S41.
58
59
Lipid Management in Patients With Diabetes or
Metabolic Syndrome

• Therapeutic lifestyle changes (TLC)
• Glycemic control
• Statin therapy to achieve LDL-C lt100 mg/dL (lt70
  mg/dL with CHD)
• TG 500 mg/dL Fibrate Omega-3 fatty
  acids
• TG 150-500 mg/dL Fibrate (with slightly low or
  normal HDL-C) Niacin (with very low HDL-C)
• TG lt150 mg/dL and Niacin
• Low HDL-C
• Well-controlled diabetes A1C lt7.0. HDL-C lt40
  mg/dL in men or lt50 mg/dL in women.

Adapted from American Diabetes Association.
Diabetes Care. 200427S68-S71. Adapted from
American Diabetes Association. Diabetes Care.
200730(suppl 1)S4-S41. Adapted from Physicians
Desk Reference. 61st ed. Montvale, NJ Thomson
PDR 20072725-2727.
59
60
Potential Cautions With Intensive Lipid Therapy
CHF congestive heart failure LV left
ventricular.
61
When Traditional Treatment Strategies Are Just
Not Enough, Is There Nothing I Can Do?
61
62
What Is LDL Apheresis?

• Treatment to remove LDL-C from the blood while
  keeping the HDL-C
• Extracorporeal procedure
• Blood taken outside of the body and returned to
  the patient without need for albumin or other
  blood products
• FDA-approved for patients1
• With homozygous familial hypercholesterolemia
  and an LDL-C level gt500 mg/dL
• With CAD and an LDL-C level 200 mg/dL or
• Without CAD but an LDL-C level 300 mg/dL

1. Gordon BR, et al. J Clin Apher.
199611128-131.
62
63
Lipid Reductions With LDL Apheresis

• Lipid/Lipoprotein Acute Reduction ()
• TC 61-71
• LDL-C 73-83
• HDL-C 3-14
• Lp(a) 53-76
• TGs 47-68

Bambauer R, et al. Ther Apher. 19971242-248.
63
64
Q A
64
65
PCE Takeaways
65
66
PCE Takeaways

• Lipid abnormalities beyond LDL-C (ie, nonHDL-C,
  TG, HDL-C) should be intensively treated to
  reduce residual CVD risk
• Fibrate monotherapy is particularly beneficial in
  reducing CVD risk in patients with metabolic
  syndrome or diabetes
• Niacin is effective therapy for reducing CVD
  risk adding niacin to statin therapy slows
  atherosclerosis progression in patients with CHD
  and reduces CVD risk
• Fibrate/statin and niacin/statin combination
  therapy correct atherogenic lipid abnormalities
  and appear to be safe

Indication not approved by FDA.
67
Based on the clinical data presented on residual
CVD risk, what percentage of your patients with
dyslipidemia would benefit from statin
combination therapy?
?
KEY QUESTION

• 25
• 26-50
• 51-75
• 76-100

Use your keypad to vote now!
67
68
Based on the clinical data presented, for
whatpercentage of your patients will you use
nonHDL-C to guide management of dyslipidemia?
?
KEY QUESTION

• 25
• 26-50
• 51-75
• 76-100

Use your keypad to vote now!
68
69
Glossary of Study Acronyms

• 4S Scandinavian Simvastatin Survival Study
• ACCORD Action to Control Cardiovascular Risk in
  Diabetes
• AFCAPS/TexCAPS Air Force/Texas Coronary
  Atherosclerosis Prevention Study
• AIM-HIGH Niacin Plus Statin to Prevent Vascular
  Events
• ASCOT-LLA Anglo-Scandinavian Cardiac Outcomes
  TrialLipid Lowering Arm
• BIP Bezafibrate Infarction Prevention
• CARDS Collaborative Atorvastatin Diabetes Study
• CARE Cholesterol and Recurrent Events
• COMPELL COMParative Effects on Lipid Levels of
  Niaspan and a Statin versus Other
  Lipid-Modifying Therapies

70
Glossary of Study Acronyms (contd)

• CPPT Coronary Primary Prevention Trial
• FHS Framingham Heart Study
• FIELD Fenofibrate Intervention and Event
  Lowering in Diabetes
• GISSI-P Gruppo Italiano per lo Studio della
  Sopravvivenza nellInfarto miocardicoPrevenzione
• HATS HDL-Atherosclerosis Treatment Study
• HHS Helsinki Heart Study
• HPS Heart Protection Study
• HPS2-THRIVE Heart Protection Study 2Treatment
  of HDL to Reduce the Incidence of Vascular
  Events
• IDEAL Incremental Decrease in End Points
  Through Aggressive Lipid Lowering
• JELIS Japan EPA Lipid Intervention Study

71
Glossary of Study Acronyms (contd)

• LIPID Long-Term Intervention with Pravastatin
  in Ischaemic Disease
• LRCS Lipid Research Clinics Prevalence
  Mortality Follow-up Study
• MRFIT Multiple Risk Factor Intervention Trial
• PROACTIVE PROspective pioglitAzone Clinical
  Trial In macroVascular Events
• PROCAM Prospective Cardiovascular Münster
• PROSPER PROspective Study of Pravastatin in the
  Elderly at Risk
• PROVE ITTIMI 22 Pravastatin or Atorvastatin
  Evaluation and Infection TherapyThrombolysis in
  Myocardial Infarction 22
• TNT Treating to New Targets
• VA-HIT Veterans Affairs High-Density
  Lipoprotein Intervention Trial
• WOSCOPS West of Scotland Coronary Prevention
  Study

72
2008
Symposia Series 2

• Doubletree Hotel Seattle Airport
• Seattle, Washington
• June 21, 2008