Oak Brook Hills Marriott Resort

1
2008
Symposia Series 1

• Oak Brook Hills Marriott Resort
• Oak Brook, Illinois
• April 5, 2008

1
1
2
DyslipidemiaWhen Statins Alone Fail

• Elizabeth Schilling, MSN, CRNP
• Adult Nurse Practitioner
• Maryland Primary Care Physicians
• Stevensville, Maryland

3
What percentage of your patients with
dyslipidemia who are receiving statin therapy
alone achieve their LDL-C goal?

• 25
• 26-50
• 51-75
• 76-100

Use your keypad to vote now!
LDL-C low-density lipoprotein cholesterol.
4
Faculty Disclosure

• Ms Schilling has no relevant financial
  relationships with any commercial interests to
  disclose

5
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

HDL-C high-density lipoprotein cholesterol.
6
Case Study
7
History and Physical Findings

• 65-year-old white man
• History of CABG surgery (1 year prior),
  hypertension
• Physical findings
• Height 1.83 m (6 ft) weight 107 kg (236 lb)
  waist circumference 103 cm (40.6 in) BMI 32
  kg/m2
• BP 118/78 mm Hg
• Current medications
• Ramipril (10 mg once daily)
• Atorvastatin (20 mg once daily)

BMI body mass index BP blood pressure CABG
coronary artery bypass graft.
8
Laboratory Results

• Lipid profile
• TC 173 mg/dL
• LDL-C 80 mg/dL
• NonHDL-C 136 mg/dL
• HDL-C 38 mg/dL
• TG 280 mg/dL
• FPG level 138 mg/dL (120 mg/dL at last visit)

FPG fasting plasma glucose TC total
cholesterol TG triglyceride.
9
What is this patients CHD risk category?

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

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CHD coronary heart disease.
10
AHA/NHLBI 2005 Scientific Statement The
Metabolic Syndrome

• Diagnosis is established by the presence of 3
  risk factors

Lower cutpoints (90 cm in men and 80 cm in
women) for Asian Americans. Or drug treatment
for elevated TG or glucose levels, hypertension,
or reduced HDL-C levels. ACE angiotensin-convert
ing enzyme AHA American Heart Association
NHLBI National Heart, Lung, and Blood Institute.
Grundy SM, et al. Circulation. 20051122735-2752.
11
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.
12
NCEP ATP III 2004 Update LDL-C Goals and
Cutpoints
In patients with moderate or higher risk, use
therapy sufficient to achieve at least a 30-40
reduction in LDL-C levels.
TLC therapeutic lifestyle changes.
Adapted from Grundy SM, et al. Circulation.
2004110227-239.
13
What would be your next step in treating this
patient?

• Increase atorvastatin dose to 40 mg once daily
• Add a glucose-lowering agent and a fibrate to his
  current atorvastatin regimen (20 mg once daily)
• Add omega-3 fatty acids(3-4 g/d) to his current
  atorvastatin regimen (20 mg once daily)
• Add extended-release niacin (1000 mg/d) to his
  current atorvastatin regimen (20 mg once daily)

Use your keypad to vote now!
14
Treatment Decision (Option 1)

• What would be your next step in treating this
  patient?
• Increase atorvastatin dose to 40 mg once daily
• Add a glucose-lowering agent and a fibrate to his
  current atorvastatin regimen (20 mg once daily)
• Add omega-3 fatty acids (3-4 g/d) to his current
  atorvastatin regimen (20 mg once daily)
• Add extended-release niacin (1000 mg/d) to his
  current atorvastatin regimen (20 mg once daily)

15
Treatment Decision (Option 1)

• Increasing the statin dose will lower LDL-C and
  nonHDL-C levels about 5-6 but will have
  minimal effect on TG and HDL-C levels
• This may have little benefit on his residual CHD
  risk

16
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
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.
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.
17
Residual CVD Risk in Patients Treated With
Intensive Statin Therapy
Statistically significant reductions, but
significant residual CVD risk remains
Moderate statin therapy
Intensive high-dose statin therapy
Patients Experiencing Major CVD Events ()
PROVE IT-TIMI 221
IDEAL2
TNT3
8888
10,001
4162
N
LDL-C (mg/dL)
104
81
101
77
95
62
Mean or median LDL-C after treatment.
1. Cannon CP, et al. N Engl J Med.
20043501495-1504 2. Pedersen TR, et al. JAMA.
20052942437-2445 3. LaRosa JC, et al. N Engl J
Med. 20053521425-1435.
18
Diminished Benefit of Lowering LDL-C
Substantially Below 100 mg/dL in High-Risk
Patients
LDL-C Level (mg/dL)
CV cardiovascular NNT number needed to
treat RRR relative risk reduction. Adapted
from Hayward RA, et al. Ann Intern Med.
2006145520-530.
19
Diminished Benefit of Lowering LDL-C
Substantially Below 100 mg/dL in High-Risk
Patients
LDL-C Level (mg/dL)
Adapted from Hayward RA, et al. Ann Intern Med.
2006145520-530.
20
Residual CVD Risk in Patients With Diabetes
Treated With Statins
CARDS2 N 2838
HPS1 n 5963
30
16
25.1
13.4
14
25
22 Risk Reduction
32 Risk Reduction
12
20.2
20
9.4
10
Major Vascular Event Rate ()
Acute CVD Event Rate ()
15
8
Residual CVD Risk
6
Residual CVD Risk
10
4
5
2
0
0
Placebo
Simvastatin
Placebo
Atorvastatin
Patients with diabetes. (HPS also enrolled
14,573 high-risk patients without diagnosed
diabetes.)
1. Collins R, et al. Lancet. 20033612005-2016
2. Colhoun HM, et al. Lancet. 2004364685-696.
21
Patients With Diabetes Have Particularly High
Residual CVD Risk After Statin Treatment
MI myocardial infarction PTCA percutaneous
transluminal coronary angioplasty.
22
Lipids in Patients With Premature CHD
Men
Women


200
177
180
Controls
160
CHD
141
139
138
140
120
Plasma Lipid Concentration (mg/dL)
100
80

60

45
35
40
20
0
LDL-C
TG
HDL-C
P lt.005 compared with controls. P lt.05 compared
with controls.
Genest JJ Jr, et al. Circulation.
1992852025-2033.
23
Independent risk factors for CVD in patients
with diabetes and the metabolic syndrome include

• 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

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24
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.
25
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.
26
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.
27
TG Level Remains CVD Risk Factor in Patients
Treated With Statins CARE and LIPID
N 13,173
Slope .018 P .02
Placebo
Pravastatin
CVD Event Rate ()
Slope .029 P lt.001
lt98
99-126
127-158
159-207
gt207
TG Level (mg/dL)
CHD death, nonfatal MI, CABG, PTCA.
Sacks FM, et al. Circulation. 20001021893-1900.
28
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 (TC -
  HDL-C) better represents the concentrations of
  all atherogenic lipoproteins than LDL-C alone
• NonHDL-C should be a secondary target of therapy
  when TG levels are 200 mg/dL

VLDL-C very low-density lipoprotein cholesterol.
NCEP ATP III. Circulation. 20021063143-3421.
29
NonHDL-C in Predicting CHD Risk

• Within nonHDL-C levels, no association was found
  between LDL-C and the risk for CHD
• In contrast, a strong positive and graded
  association between nonHDL-C and risk for CHD
  occurred within every level of LDL-C
• NonHDL-C is a stronger predictor of CHD risk
  than LDL-C

Relative CHD Risk
190
160-189
lt160
lt130
130-159
160
NonHDL-C (mg/dL)
LDL-C (mg/dL)
Liu J, et al. Am J Cardiol. 2006981363-1368.
30
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.
31
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.
32
Low HDL-C Increases CVD Risk Even if LDL-C
Levels Are Well ControlledTNT Study
On-treatment level (3 months).
Barter P, et al. Poster presented at American
College of Cardiology 55th Annual Scientific
Session March 11-14, 2006 Atlanta, Ga.
Abstract 914-203.
33
CVD Risk Associated With Low HDL-C Level Remains
in Patients Treated With Statins
Low HDL-C statin
High HDL-C statin
CVD Event Rate ()
CVD Event Rate ()
Sacks FM, et al. Circulation. 20001021893-1900.
HPS Collaborative Group. Lancet. 20023607-22.
34
In patients with diabetes who receive statin
therapy to reduce LDL-C levels

• 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

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35
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

36
Treatment Decision (Option 2)

• What would be your next step in treating this
  patient?
• Increase atorvastatin dose to 40 mg once daily
• Add a glucose-lowering agent and a fibrate to his
  current atorvastatin regimen (20 mg once daily)
• Add omega-3 fatty acids (3-4 g/d) to his current
  atorvastatin regimen (20 mg once daily)
• Add extended-release niacin (1000 mg/d) to his
  current atorvastatin regimen (20 mg once daily)

37
Treatment Decision (Option 2) 3-Month Follow-up

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

38
Treatment Decision (Option 2) 3-Month
Follow-up (contd)

• After 3 months therapy with atorvastatin plus
  fenofibrate and a glucose-lowering agent

39
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.
40
American Diabetes Association 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.
41
Lipid Management in Patients With Diabetes or
Metabolic Syndrome

• 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.
42
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.
1Manninen V, et al. Circulation.
19928537-45. 2Keech A, et al. Lancet.
20053661849-1861. 3Tenenbaum A, et al. Arch
Intern Med. 20051651154-1160. 4Rubins HB, et
al. Arch Intern Med. 20021622597-2604.
43
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.
44
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 Events (Primary End Point)
Nonfatal MI
CHD Death
Coronary Revascularization
Nonfatal MI and CHD death. CHD events, stroke,
CVD death, revascularizations.
Keech A, et al. Lancet. 20053661849-1861.
45
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.
46
Treatment Decision (Option 3)

• What would be your next step in treating this
  patient?
• Increase atorvastatin dose to 40 mg once daily
• 2. Add a glucose-lowering agent and a fibrate to
  his current atorvastatin regimen (20 mg once
  daily)
• 3. Add omega-3 fatty acids (3-4 g/d) to his
  current atorvastatin regimen (20 mg once daily)
• 4. Add extended-release niacin (1000 mg/d) to his
  current atorvastatin regimen (20 mg once daily)

47
Treatment Decision (Option 3)

• Prescription omega-3 fatty acids at 3-4 g/d are
  indicated for patients with severe
  hypertriglyceridemia (TG gt500 mg/dL)
• This reduces TG up to 40, but there is little
  change in HDL-C levels, and LDL-C levels may
  increase

48
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.
49
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.
50
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.
51
Treatment Decision (Option 4)

• What would be your next step in treating this
  patient?
• Increase atorvastatin dose to 40 mg once daily
• Add a glucose-lowering agent and a fibrate to his
  current atorvastatin regimen (20 mg once daily)
• Add omega-3 fatty acids (3-4 g/d) to his current
  atorvastatin regimen (20 mg once daily)
• Add extended-release niacin (1000 mg/d) to his
  current atorvastatin regimen (20 mg once daily)

52
Treatment Decision (Option 4)3-Month
Follow-up

• Visit 1
• TLC (diet, exercise) reinforced
• Glucose-lowering agent and extended-release
  niacin (1000 mg at bedtime) prescribed as add-on
  to statin therapy
• Visit 2
• Improvements in lipid profile and glucose level
• No musculoskeletal side effects no hepatic or
  renal laboratory abnormalities

53
Treatment Decision (Option 4)3-Month Follow-up
(contd)

• After 3 months therapy with atorvastatin plus
  extended-release niacin and a glucose-lowering
  agent

54
CDP Macrovascular Outcomes
15 Reduction P lt.05
Placebo (n 2789)
Niacin (n 1119)
26 Reduction P lt.05
24 Reduction P lt.05
Event Rate ()
47 Reduction P lt.05
CHD Death/ Nonfatal MI
Nonfatal MI
Stroke/TIA
CV Surgery
Total follow-up experience (mean, 6.2
years) 5-year incidence TIA transient ischemic
attack.
CDP Research Group. JAMA. 1975231360-381.
55
CDP Reduction in Recurrence of MI by Baseline
FPG Level
Placebo
Interactive P value NS
Niacin
30 Reduction
57 Reduction
25 Reduction
24 Reduction
Nonfatal MI Event Rate ()
lt95
95-104
105-125
126
Baseline FPG Level (mg/dL)
6-year follow-up. American Diabetes Association
definition of diabetes.
Canner PL, et al. Am J Cardiol. 200595254-257.
56
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)
Lp(a) lipoprotein (a) niacin ER niacin
extended-release. McKenney JM, et al.
Atherosclerosis. 2007192432-437.
N 292 12 weeks. P lt.05 vs atorvastatin
niacin ER.
57
Fibrate/statin combination therapy has the
potential to increase the risk of

• Arrhythmia
• Myopathy
• Osteoporosis
• Thrombosis

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58
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.
59
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.
60
Safety of Lovastatin/Niacin ER and Niacin ER vs
Statin Monotherapy (FDA-AERS)

P lt.05 versus L/N

Serious AERs Per Million Prescriptions
L/N
N
L
A
S
P

Liver AERs Per Million Prescriptions
Rhabdomyolysis AERs Per Million Prescriptions
L/N
N
L
A
S
P
L/N
N
L
A
S
P
A atorvastatin AERs adverse event reports
FDA-AERS US Food and Drug Administration
Adverse Event Reporting System L lovastatin N
niacin ER P pravastatin S simvastatin.
Alsheikh-Ali AA, et al. Am J Cardiol.
200799379-381.
61
Ongoing Trials With Fibrate/Statin or
Niacin/Statin Combination Therapy
CIMT carotid artery intima media thickening.
62
Q A
63
PCE Takeaways
64
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.
65
Based on the clinical data presented on residual
CVD risk, what percentage of your patients with
dyslipidemia would benefit from statin
combination therapy?

• 25
• 26-50
• 51-75
• 76-100

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66
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
• CDP Coronary Drug Project
• COMPELL COMParative Effects on Lipid Levels of
  Niaspan and a Statin versus Other Lipid-Modifying
  Therapies

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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
• 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
• LIPID Long-Term Intervention with Pravastatin
  in Ischaemic Disease

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Glossary of Study Acronyms (contd)

• LRCS Lipid Research Clinics Prevalence
  Mortality Follow-up Study
• MRFIT Multiple Risk Factor Intervention Trial
• 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

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2008
Symposia Series 1

• Oak Brook Hills Marriott Resort
• Oak Brook, Illinois
• April 5, 2008

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