management of hypertriglyceridemia sponsored by access medical group department of continuing...

Management of Hypertriglyceridemia

Sponsored by

ACCESS Medical Group

Department of Continuing Medical Education

Funded by an unrestricted educational grant from Abbott Laboratories.

© 2001 ACCESS Medical Group

Atherosclerosis Prevention Trials

The Pyramid of Recent Trials

4S

CARE

WOSCOP

Relative Size of the Various Segments of the Population

AFCAPS/TexCAPS

LIPID

Very high cholesterol with CHD or MI

Moderately high cholesterol in high risk CHD or MI

Normal cholesterol with CHD or MI

High cholesterol without CHD or MI

No history of CHD or MI

4S: Evaluating LoweringCholesterol on Coronary Events

• Baseline total cholesterol levels: 210-310 mg/dL

• High-risk group (high LDL, prior MI or angina)

• Reduction of LDL levels: 35%

• Reduction of major coronary events: 34%

• Reduction of total mortality: 30%

Patients with CHD and Hypercholesterolemia

End of the cholesterol controversy4S Group. Lancet. 1994;344:1383-1389.

Coronary Events Definedby Baseline LDL-C

CARE suggests a lower boundary for a clinically important influence of the LDL level on CHD.

Sacks FM, et al. N Engl J Med. 1996;335:1001-1009.

Change in RiskVariable N Patients N (%) Patients with event

LDL-C Placebo Pravastatin PravastatinPlacebo 95% (CI)

125-150 mg/dL

150-175 mg/dL

125 mg/dL

441

1172

465

410

1183

488

93 (21)

311 (27)

145 (31)

89 (22)

239 (20)

102 (21)

+3%

-26%

-35%

No risk reduction in patients with LDL levels under 125 mg/dL.

Reduction in LDL Cholesteroland Coronary Events1,2,3

1. 4S Group. Lancet. 1994;344:1383-1389. 2. WOSCOPS Group. Circulation. 1998;97:1440-1445.

3. Frick MH, et al. N Engl J Med. 1987;317:1237-1245.

-50

-40

-30

-20

-10

0

4S WOSCOPS Helsinki

LDL

CoronaryEvents

Perc

ent R

educ

tion

Lowering cholesterol is effective and safe in hypercholesterolemic patients with evidence of CHD and leads to a

reduction in coronary events.

4S Group. Lancet. 1994;344:1383-1389.

• LDL reduction in primary and secondary prevention can significantly reduce clinical cardiac events

• It can also significantly reduce the rate of arteriographically defined disease progression

LDL Reduction and CHD RiskThe latest studies have confirmed the positive correlation

between CAD risk and lowering cholesterol

However, elevated LDL is only one of several factors contributing to CAD risk

BeyondLDL

Beyond LDL ReductionThere is something more than LDL

• Such a large number of poor responders implicates factors other than just LDL in the development or progression of CHD (ie, low HDL, small, dense LDL, fibrinogen, Lp(a), triglycerides)

• Aggressively treating other important risk factors, such as low HDL, may further benefit patients

Superko HR. Circulation. 1996;94:2351-2354.

StudyControl GroupClinical Events

Treatment GroupClinical Events

% Reduction Clinical Events

622 (28.0%)

248 (7.5%)

431 (19.4%)

174 (5.3%) 31.0%

30.6%4S

WOSCOPS

CHD Risk Factors Beyond LDL

• Triglycerides

• HDL

• Small, dense LDL

• Apo CIII

• Lp(a)

• Homocysteine

• Fibrinogen

The Role of

Triglyceridesas a CHD Risk Factor

Possible Atherogenic Changes Accompanying Hypertriglyceridemia

Hypertriglyceridemia

Increasedchylomicron

remnants

Small,dense LDL

Coagulationchanges

Increased VLDL cholesterol-rich

remnantsLow HDL

Miller M. Eur Heart J. 1998;19(Suppl H):H18-H22.

Development of Hypertriglyceridemia

Liver

VLDLChylomicron

Intestine

DefectiveLipolysis

Remnants

Miller M. University of Maryland, unpublished data, 1998.

Risk of CHD by Triglyceride Level(The Framingham Heart Study)

N=5127

Castelli WP. Am J Cardiol. 1992;70: 3H-9H.

0

0.5

1

1.5

2

2.5

3

50 100 150 200 250 300 350 400

Men Women

Rel

ativ

e R

isk

Triglyceride Level (mg/dL)

The Copenhagen Male Study• 2906 white men• Age range: 53-74 years• Initially free of overt cardiovascular disease• 8-year follow-up period• 229 men had first IHD event• Triglyceride tertile cut points: 96.6 mg/dL and 141.8 mg/dL• Crude cumulative incidence rates of IHD: 4.6% for lowest, 7.7%

for middle, 11.5% for highest third (for the trend, P<0.001)

Jeppesen J, et al. Circulation. 1998;97:1029-1036.

The Copenhagen Male StudyAdjusted IHD Incidence Rates

N=2906

Jeppesen J, et al. Circulation. 1998;97:1029-1036.

Adjusted for• Age• Body mass index• Alcohol use• Smoking• Physical activity• Hypertension• NIDDM• Social class• LDL• HDL

0

0.5

1

1.5

2

2.5

Lowest Middle Highest

Com

pare

d W

ith

Low

est T

erti

le

Tertile of Triglyceride Level

Baltimore Coronary Observational Long-Term StudyTriglycerides Compared With Survival Rates

Eve

nt F

ree

Surv

ival

(%

)

Time (mo) Following 1977-78 Coronary Arteriogram

TG <100 mg/dL (n=114)TG >100 mg/dL (n=236)P=0.008

Miller M, et al. J Am Coll Cardiol. 1998;31:1252-1257.

Cum

ulat

ive

Perc

ent

Freq

uenc

y

Triglyceride (mg/dL)

Phenotype A

Phenotype B

Austin M, et al. Circulation. 1990;82:495-506.

Distribution of Adjusted Plasma TriglyceridesLDL Phenotype A and B

Increase in CVD RiskDue to High Triglycerides

(Univariate Analysis)

0%

20%

40%

60%

80%

100%

Men Womenn=46,413 n=10,864

30%

75%

Hokanson JE, et al. J Cardiovasc Risk. 1996;3(2):213-219.

Relative risks and 95% CI calculated and standardized with respect to a1 mmol/L increase in triglyceride.

The Role of

HDL-Cholesterolas a CHD Risk Factor

HDL: A Major Risk Factor for CHD

• A low plasma HDL is an important risk factor for CHD in the general population

• A high level of HDL may confer cardioprotection

• Reverse cholesterol transport by HDL may be the principle cardioprotective mechanism

On average, a 10% decrease in CHD risk occurs for each increase of 4 mg/dL in the HDL level.

The ILIB Lipid Handbook for Clinical Practice. 1995:26.

HDL: Major Factorin Predicting Reduced CAD

0

20

40

60

80

100

120

<35 35 - 55 >55

HDL-cholesterol (mg/dL)

Inci

denc

e of

CH

D (

per

1000

in 6

yea

rs)

Assmann G, et al. Atherosclerosis. 1996;124(suppl):S11-S20.

N=4407

HDL Predictive Value(The Framingham Heart Study)

0

5

10

15

<40 40-49 50-59 >59

<200200-230

231-260>260

Men and women without CHD history

HDL-cholesterol (mg/dL) Total-ch

olester

ol (mg/dL)

Inci

denc

e (%

in 4

yea

rs)

Castelli WP. JAMA. 1986;256(20):2835-2838.

LDL and HDL Impact on CHD RiskA Compounded Rather Than Additive Impact

0

100

200

300

400

<35 35-55 >55

<135

135-154

155-195

>195

HDL-cholesterol (mg/dL)LDL-ch

olester

ol (mg/dL)

Inci

denc

e pe

r10

00 (

in 6

yea

rs)

Assmann G, et al. Atherosclerosis. 1996;124(suppl):S11-S20.

HDL in Clinical Practice

• Routinely measured in all adult patients

• HDL-C <35 mg/dL is a major risk factor

• Nonpharmacologic therapy (exercise, weight loss, smoking cessation)

• Pharmacologic therapy

Consider drug therapy that lowers LDL-C and also increases HDL-C levels.

Expert Panel. JAMA. 1993;269:3015-3023.

The Role of

Small, Dense LDLas a CHD Risk Factor

Small, Dense LDL

• Dangerous: Small, dense LDL trait increases heart disease risk up to three fold

• Common: 40% to 50% of men with heart disease have small, dense LDL

• Measurable: Tests are now available to physicians

• Treatable: Approaches can involve lifestyle changes and/or drugs

The ILIB Lipid Handbook for Clinical Practice. 1995:26.

Austin MA, et al. JAMA. 1988;260(13):1917-1921.

Atherogenicity of Small, Dense LDL

Evidence from in vitro studies suggests that large, buoyant LDL particles are more resistant to oxidative stress and small, dense LDL particles more susceptible to oxidation.

EndothelialChemoattractants

Foam Cell

Highly oxidizedSmooth Muscle

Cell

Mildly oxidized

Macrophage

LDL

LDL

Endothelium Monocyte

Macrophage

Small, Dense LDL and Drug Therapy

• In a trial measuring the effects of simvastatin on ApoB metabolism and LDL subfraction distribution, it was found that small, dense LDL were not significantly affected.

Gaw A, et al. Arterioscler Thromb. 1993;13:170-189.

• In a study investigating the ability of pravastatin to affect small, dense LDL, it was found that although this agent favorably altered total cholesterol and LDL levels, the abnormal LDL particle distribution and composition were not affected.

Franceschini G, et al. Arterioscler Thromb. 1994;14:1569-1575.

The Role of

Fibrinogenas a CHD Risk Factor

Elevated Plasma FibrinogenA Major, Independent Cardiovascular Risk Factor

• Epidemiological studies

• Cross-sectional analyses

• Clinical cohort studies

There is a sizeable body of evidence identifying fibrinogen as a major, independent cardiovascular risk factor

Ernst E, et al. Eur Heart J. 1995;16(supplA):47-53.

Fibrinogen and AtherosclerosisN=652 men

0%

20%

40%

60%

80%

100%

Lower Middle Upper

Present

Absent

Pres

ence

or

Abs

ence

of P

laqu

e

Levenson J, et al. Arterioscler Thromb Vasc Biol. 1995;15:1263-1268.

Effects of Lipid-Lowering Agents on Fibrinogen

1

-16

-10

20

40

-30

-20

-10

0

10

20

30

Diet* Feno** Beza** Gem** Simva* Prava*

Cha

nge

in F

ibri

noge

n (%

)

Branchi A, et al. Thromb Haemost. 1993;70:241-243.

*Not significant

**P<0.01

Fibrate Clinical Overview

Fenofibrate

Bezafibrate

Gemfibrozil

CH3

CH3

O CH2 CH2 CH2 CH2

CH3

COOH

CH3

C

C O

O

C

CH3

COO CH

CH3

CH3

Cl

CH3

Fibrates

OO

O

OH

CH3H3C

Cl

NH

Metabolic Action of Fibrates

Lipoprotein lipase

VLDLIDL

Apo C-II Apo C-III

Chylomicrons

Liver

Packard CJ. Eur Heart J. 1998;19(suppl A):A62-A65.

Apo EApo C-III

FFA

Fibrate

PPAR

Nucleus

HNF-4 +ve factor

CIII GeneC3P

Plasma Apo C-III 60%

Apo E/Apo C-III

Packard CJ. Eur Heart J. 1998;19(suppl A):A62-A65.

Metabolic Action of FibratesThe Peroxisome Proliferator Activator Receptor (PPAR)

-

-

Mechanisms of Action of Fibrates• Inhibit triglyceride synthesis; reduces VLDL release into

circulation• Increase lipoprotein lipase activity, which catabolizes

chylomicrons and VLDL• Increase catabolism of triglyceride-rich VLDL, thereby lowering

serum VLDL levels• Increase HDL through improved Apo A-I and Apo A-II synthesis

Serum VLDL(Triglyceride-rich)

Fibrate

......... ..

.. . .....

Lowered Serum VLDL(Reduced triglycerides)

Before After Percent(mean ± SE) ( mean ± SE) Changes* P

Fenofibrate for the Treatment of Type IV and V HyperlipoproteinemiasA Double-Blind, Placebo-Controlled Multicenter US Study

Goldberg AC, et al. Clin Ther. 1989;11:69-83.

Fenofibrate

251.8 ± 5.3

92.1 ± 6.8

128.4 ± 7.1

33.7 ± 1.1

432.0 ± 19.1

349.8 ± 34.3

227.4 ± 6.7

45.8 ± 4.5

136.7 ± 5.3

40.3 ± 1.9

223.4 ± 13.9

177.8 ± 24.6

-9.1

-44.7

NS

+19.6

-46.2

-44.1

*These are mean percentage changes, not percentage changes in means.

NS=Not statistically significant when compared with placebo (12% increase).

Total cholesterol

VLDL-cholesterol

LDL-cholesterol

HDL-cholesterol

Total triglyceride

VLDL-triglyceride

<0.001

<0.001

0.8570

0.0014

<0.001

<0.001

Group A(350-499 mg/dL)



Fenofibrate

261.0 ± 6.7

126.2 ± 7.0

103.1 ± 6.8

29.6 ± 1.3

725.6 ± 37.4

543.3 ± 50.8

223.3 ± 6.6

53.7 ± 3.4

131.0 ± 6.0

36.0 ± 1.8

308.0 ± 19.9

204.7 ± 23.0

-13.8

-49.4

+45.0

+22.9

-54.5

-50.6

*These are mean percentage changes, not percentage changes in means.

Total cholesterol

VLDL-cholesterol

LDL-cholesterol

HDL-cholesterol

Total triglyceride

VLDL-triglyceride

Before After Percent (mean ± SE) ( mean ± SE) Changes* P

0.0001

0.0001

0.0002

0.0029

0.0001

0.0001

Group B(500-1500 mg/dL)


• Many patients with markedly elevated triglycerides have reduced LDL levels because of a derangement in the normal composition of LDL

• This derangement produces a triglyceride-rich and cholesterol-depleted LDL

• When triglycerides are reduced with therapy, the composition of LDL normalizes; this change can elevate LDL levels


Fenofibrate for the Treatment ofType IV and V HyperlipoproteinemiasA Double-Blind, Placebo-Controlled Multicenter US Study

Week of Treatment

-60

-50

-40

-30

-20

-10

0

10

20

0 2 4 6 8

Placebo

Fenofibrate

% C

hang

e fr

om B

asel

ine


Total Triglyceride - Group B


Week of Treatment


-10

-5

0

5

10

15

20

25

30

0 2 4 6 8

Placebo

Fenofibrate% C

hang

e fr

om B

asel

ine

HDL-C - Group B


“[F]enofibrate is both safe and effective in the treatment of primary type IV and V hyperlipoproteinemias in patients in whom dietary modifications have proved ineffective in reducing plasma triglycerides.”

Goldberg AC, et al. Clin Therapeut. 1989;11:69-83.

Effects of Fenofibrate on Plasma LipidsDouble-Blind, Multicenter Study in Patients

with Type IIa or IIb Hyperlipidemia

Brown WV, et al. Arteriosclerosis. 1986;6:670-678.

N=227Variable Fenofibrate PlaceboSample Size (n) 116 111

Age (yr ± SD)Weight (lbs ± SD)Sex (n)

MaleFemale

Race (n)CaucasianBlackHispanicOther

Hyperlipoproteinemia (n)Type IIaType IIb

52.0 ± 0.96 51.7 ± 0.97 165.1 ± 2.48 164.9 ± 2.49

8234

7140

104606

98922

9224

8922

Percentage Changes at Endpoint from Baseline Values after 24 Weeks of Double Blind Study vs Placebo (Plb)

Total Cholesterol -17.5 -0.4 -15.8 +4.6

LDL Cholesterol -20.3 +0.4 -6.1 -0.5

HDL Cholesterol +11.1 -1.2 +15.3 -3.5

Total Triglycerides -37.9 -4.2 -44.6 +22.3

LDL/HDL Cholesterol -27.1 -1.9 -13.3 0.0

VLDL Cholesterol -38.4 -2.5 -52.7 +8.4

Feno Plb Feno Plbn=92 n=88 n=24 n=22

Type IIa (%) Type IIb (%)


with Type IIa or IIb Hyperlipidemia

Brown WV, et al. Arteriosclerosis. 1986; 6:670-678. P<0.01 except for LDL-C in Type IIb, where P>0.10


with Type IIa or IIb HyperlipidemiaMean LDL Plasma Cholesterol Concentration


Type IIa

150

170

190

210

230

0 2 4 8 12 18 24

Fenofibrate

Placebo

Double-Blind PeriodM

ean

Con

cent

rati

on (

mg%

)

Weeks on Study Medication


with Type IIa or IIb HyperlipidemiaMean LDL Plasma Cholesterol Concentration


Type IIb

150

160

170

180

190

200

210

0 2 4 8 12 18 24

Fenofibrate

Placebo

Double-Blind Period

Mea

n C

once

ntra

tion

(m

g%)

Weeks on Study Medication

Comparative Efficacy and Safety of Micronized Fenofibrate and Simvastatin in Patients with

Primary Type IIa or IIb Hyperlipidemia

Study Design

Farnier M, et al. Arch Int Med. 1994;154:441-449.

• Single-center, Double-blind, Crossover Trial

• 60 Patients (32 type IIa and 28 type IIb)

• Randomized to treatment for 3 months

• Single daily dose of fenofibrate 200 mg or simvastatin 20 mg

• Changed to alternative treatment for a further 3 months



(Randomized, Crossover Study)


Fenofibrate200 mg/day

Simvastatin20 mg/day

Simvastatin20 mg/day

Fenofibrate200 mg/day

Type IIa, n=16Type IIb, n=14

Type IIa, n=16Type IIb, n=14

Group 1

Group 2

I I I I I I I0 3 6

Months



Characteristic Fenofibrate SimvastatinSample Size (n) 30 30

Age (yr ± SD)Weight (lbs ± SD)Sex (n)

malefemale

Hyperlipoproteinemia (n)Type IIaType IIb

Total Cholesterol (mg/dL)LDL-C (mg/dL)HDL-C (mg/dL)Triglyceride (mmol/L)

41.5 ± 11.4 46.1 ± 10.2 149.6 ± 23.5 159.1 ± 27.9

1614

219

1614

1614

315 ± 50 323 ± 45234 ± 48 241 ± 5050 ± 18 48 ± 11

1.82 ± 1.19 1.91 ± 1.17


-28 -28

-34-36 -37

-50

-40

-30

-20

-10

0

Total-C LDL-C HDL-C Trig

FenofibrateSimvastatin

Fenofibrate Versus SimvastatinEffect on Overall Lipid Profile


(Type IIa)%

Cha

nge

from

Bas

elin

e

NC NC NC

NC=No change

-23 -21 -25 -30

29

17

-52

18

-60

-45

-30

-15

0

15

30

45

Total-C LDL-C HDL-C Trig

FenofibrateSimvastatin

Fenofibrate Versus SimvastatinEffect on Overall Lipid Profile


(Type IIb)%

Cha

nge

from

Bas

elin

e

Fenofibrate and Plaque Regression

• 21 Patients with CHD had 98 narrowings

• Mean duration of follow-up: 21 months (range 12 to 36 months)

• Comparison with a similar untreated group of 21 patients with CHD presenting 98 narrowings

• Quantitative coronary angiography (QCA)

Hahmann HW, et al. Am J Cardiol. 1991;67: 957-961.

Fenofibrate and Plaque RegressionPe

rcen

t Pat

ient

s

Hahmann HW, et al. Am J Cardiol. 1991;67:957-961.

0

10

20

30

40

50

60

70

Fenofibrate Untreated

RegressionStabilizationProgression

Micronized Fenofibrate A Comprehensive Profile

Kornitzer M, et al. Atherosclerosis. 1994;110(suppl):S49-S64.

-30

-15

0

15

30

45

TC LDL HDL Fibrinogen

NormalHigh Risk*

Perc

ent C

hang

eN=1545 patients

*High risk: TC 250 mg/dL, LDL 185 mg/dL, HDL 35 mg/dL, fibrinogen 300 mg/dL

LDL Profile of Fenofibrate

-60%

-40%

-20%

0%

20%

40%

60%

Caslake MJ, et al. Arterioscler Thromb. 1993;13:702-711.

Cha

nge

Total Cholesterol

LDL-C LDL Receptor Uptake

Large, Buoyant LDL

Small, Dense LDL

The Helsinki Heart Study

• A 5-year trial that tested the efficacy of gemfibrozil for decreasing the risk of coronary artery disease in hypercholesterolemic men without coronary artery disease

• The study involved 4081 men (40 to 55 years of age) with a non-HDL cholesterol level >200 mg/dL

• Gemfibrozil use was associated with a 34% reduction in coronary artery events

Frick MH, et al. N Engl J Med. 1987:317:1237-1245.

Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA HIT)

Study Design

Rubins HB, et al. N Engl J Med. 1999;341:410-418.

• Double-blind trial that compared gemfibrozil (1200 mg/day) with placebo

• Study of 2531 men with coronary heart disease, high-density lipoprotein cholesterol levels 40 mg/dL, and low-density lipoprotein cholesterol levels 140 mg/dL

• The primary outcome was nonfatal myocardial infarction or death from coronary causes


Age (yr) 64 ± 7 64 ± 7Age >60 years (%) 77 76Prior MI (%) 61 61Time since MI (yr) 6 ± 6 6 ± 6Diabetes (%) 25 24Hypertension (%) 57 57Low-density lipoprotein, mg/dL (mean) 112 ± 23 111 ± 22 High-density lipoprotein, mg/dL (mean) 32 ± 5 32 ± 5

Triglycerides, mg/dL (mean) 160 ± 67 161 ± 68

Placebo GemfibrozilCharacteristic (N=1267) (N=1264)

The Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA HIT): Baseline Characteristics


The Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA HIT) Results

0

5

10

15

20

25

30

Placebo Gemfibrozil

*

* Risk reduction = 24% (P<0.001)

% W

ith D

eath

, M

yoca

rdia

l In

farc

tion,

or

Str

oke

The Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA HIT): Summary

• VA HIT compared treatment with gemfibrozil or placebo in 2531 men with coronary heart disease and low levels of high-density lipoprotein cholesterol

• There was a 24% reduction in risk of nonfatal myocardial infarction, stroke, or death due to CHD in the group who received gemfibrozil (P<0.001)

• The findings suggest that the rate of coronary events is reduced by raising HDL and lowering triglycerides without lowering LDL


Double-blind, randomized, placebo-controlled angiographic study using 200 mg/day micronized fenofibrate

Population• 305 men, 113 women, 40 to 65 years of age• Subjects had type 2 diabetes with good glycemic control, and at least one

visible coronary lesion• Mild dyslipoproteinemia typically seen in type 2 diabetes• Half of subjects had no previous clinical coronary disease• Treatment period at least 3 years

Primary Aim• To determine by quantitative angiography whether correcting lipid

abnormalities with fenofibrate in type 2 diabetes alters the progression of coronary artery disease

Steiner G. Diabetologia. 1996;39:1655-1661.

The Diabetes Atherosclerosis Intervention Study (DAIS) Protocol

The Diabetes Atherosclerosis Intervention Study (DAIS)Baseline Clinical Characteristics

Placebo Fenofibrate

(n=211) (n=207)Demographics Age (years ± SD) 56 ± 6 57 ± 6 Women (%) 26 28 Current smokers (%) 16 14

Blood pressure History of Hypertension (%) 48 55 Systolic (mm Hg ± SD) 140 ± 18 140 ± 19 Diastolic (mm Hg ± SD) 81 ± 9 82 ± 9

Coronary Disease History of CAD (%) 47 48 Prior intervention (%) 30 32

DAIS Investigators. Lancet. 2001;357:905-910.

The Diabetes Atherosclerosis Intervention Study (DAIS)Angiographic Changes from Baseline

Minimum LumenDiameter

0.000.00

-0.02-0.02

-0.04-0.04

-0.06-0.06

-0.08-0.08

-0.10-0.10

mmmm

-40%-40%

P = 0.029Prog

ress

ion

of C

AD

% % ChangeChange

Percent Stenosis

4.004.00

2.002.00

0.000.00

P = 0.020

-42%-42%

Mean Segment Diameter

0.000.00

-0.02-0.02

-0.04-0.04

-0.06-0.06

-0.08-0.08

-0.10-0.10

mmmm

-25%-25%

P = 0.171

DAIS Investigators. Lancet. 2001;357:905-910.PlaceboFenofibrate

The Diabetes Atherosclerosis Intervention Study (DAIS)Combined Clinical Endpoints

Placebo Fenofibrate 0

5

15

Eve

nt R

ate

(%)

Eve

nt R

ate

(%)

25

20

10

-23%*

* DAIS was not powered to examine clinical events. Even though the results suggest a trend, they were not statistically significant.

Participants with at least one clinical or interventional endpoint, including death, stroke, MI, CABG, PTCA, and hospitalization for angina.


DAIS assessed the effects on coronary atherosclerosis of correcting lipoprotein abnormalities in patients with type 2 diabetes

The study found that treatment with fenofibrate reduced the angiographic progression of coronary artery disease in men and women with type 2 diabetes; this effect was related, at least in part, to the correction of lipoprotein abnormalities

DAIS findings suggest that people with type 2 diabetes should have lipoproteins measured at diagnosis and annually thereafter

Existing evidence suggests that any lipoprotein abnormality should be corrected, even if small, to reduce the risk of coronary disease in patients with type 2 diabetes

The Diabetes Atherosclerosis Intervention Study (DAIS)Clinical Implications


The Diabetes Atherosclerosis Intervention Study (DAIS)Comparison to Clinical Trials With Diabetic Patients

Study AgentEvent

Reduction

DAIS Fenofibrate 23%

CARE Pravastatin 25%

LIPID Pravastatin 19%

VA HIT Gemfibrozil 24%

P Value

NS

NS = Not statistically significant

0.05

NS

<0.001


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