nhlbi/nei national institutes of health

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NHLBI/NEI

National Institutes of Health

NHLBI/NEI

National Institutes of Health

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Diabetes & CVD

• Patients with type 2 diabetes

• 2 to 4 X increased risk of CVD

• Question: What is value of intensive control of CVD risk factors in reducing CVD rates?

• Glycemia• Lipids (HDL-C/TG)• Systolic Blood Pressure

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Overall Goal for ACCORD

To test three complementary medical

treatment strategies for type 2

diabetes to enhance options for

reducing the very high rate of major

CVD morbidity and mortality

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The Three Medical Strategies(Three Trials in One)

• Intensive glycemic control• A1C < 6% versus 7.0%-7.9%

• Treatment to increase HDL-C and lower TG (in context of good LDL-C and glycemia control)

• Fenofibrate + Simvastatin versus Simvastatin

• Intensive blood pressure control (in context of good glycemia control)

• SBP < 120 mmHg versus SBP < 140 mmHg

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Double 2 x 2

IntensiveGlycemicControl

5000

StandardGlycemicControl

5000

Lipid BP

Fibrate Placebo Intensive Std

210021002900 2900

1450 1450

14501450

1050

10501050

1050

10,000

42005800

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Primary Outcome Measure

First occurrence of a major cardiovascular disease event:

• Nonfatal MI

• Nonfatal Stroke

• Cardiovascular Death

MI’s, Strokes, and Deaths adjudicated by a committee masked to treatment assignment

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Other ACCORD Outcomes

• Other cardiovascular outcomes

• Total mortality

• Microvascular outcomes

• Health-related Quality of Life (subset)

• Cost-effectiveness (subset)

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ACCORD Eye Study

National Eye Institute

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• important primary endpoint• common cause of vision loss• medical management crucial• standard of care: yearly

dilated eye exams

Diabetic Retinopathy

ACCORD Eye Study Rationale

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• important primary endpoint• DCCT – Primary outcome• UKPDS – Composite primary

outcome

Diabetic Retinopathy

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Diabetes Control and ComplicationsTrial (DCCT)

Randomized Clinical Trial

Intensive Blood Glucose Controlvs.

Conventional Blood Glucose Control

Type 1 Diabetes

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0

10

20

30

40

50

60

0 2 4 6 8 10

Primary Intervention - 3 Step Change

Years

PercentWith Event

DCCT Results

ConventionalIntensive

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0

10

20

30

40

50

60

0 2 4 6 8 10

Secondary Intervention - 3 Step Change

Years

PercentWith Event

DCCT Results

ConventionalIntensive

14

0

0.5

1

1.5

2

2.5

0 1 2

Secondary Intervention - 3 Step Change

Years

PercentWith Event

DCCT Results

P < 0.02

ConventionalIntensive

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Results of Intensive Therapy:

• Clinically Important Retinopathy (34-76%)

• Photocoagulation (34%)

• First Appearance of Retinopathy (27%)

DCCT Summary

Reduction in Retinopathy

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Further Retinopathy Progression from the Level at DCCT Closeout

Adjusted For DCCT Closeout Level

02

46

810

1214

1618

20

1 2 3 4

Per

cen

tage

Years of follow-up in EDIC

Conventional RxConventional Rx

Tight Control RxTight Control Rx

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Randomized Clinical Trial

Intensive Blood Glucose Controlvs.

Conventional Blood Glucose Control

U K Prospective Diabetes Study

Type 2 Diabetes

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U K Prospective Diabetes StudyMicrovascular Endpoints

10%

30%

20%

6 930 1512

Years

Conventional

Intensive

0%

Event Rate

Photocoagulation/VHRenal Failure/DeathMyocardial Infarction

p=0.0099

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U K Prospective Diabetes StudyRetinopathy - 2 Step Progression

10%

30%

40%

20%

6 930 12Years

Conventional

Intensive

50%

0%

Event Rate

p=0.78 p=0.02 p=0.01 p=0.01

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Randomized Clinical Trial

Intensive Blood Pressure Controlvs.

Conventional Blood Pressure Control

U K Prospective Diabetes Study

Type 2 Diabetes

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U K Prospective Diabetes StudyBlood Pressure by Treatment Group

mm Hg

100

80

120

140

160

3 6 90

Years1 2 4 5 87

Less Tight - Systolic

More Tight - Systolic

Less Tight - Diastolic

More Tight - Diastolic

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Retinopathy - 2 Step Progression

10%

30%

40%

20%

6 930 12

Years

Less Tight BP Control

More Tight BP Control

50%

0%

Event Rate

UKPDS Blood Pressure Trial

P=0.38 P=0.02 P=0.004

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Serum Cholesterol

Diabetic Retinopathy

and

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Early Treatment Diabetic

Retinopathy Study (ETDRS)

Wisconsin Epidemiologic Study of

Diabetic Retinopathy (WESDR)

Serum cholesterol

Observational Data

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Doubled the risk of retinal hard

50% increased risk of moderate vision

50% increased risk of developing hard exudate at baseline

Serum cholesterol-ETDRS Results

Elevated levels:

exudate during follow-up

loss at 5 years

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to assess the rates of progression of

medical treatment on diabetic retinopathy

To evaluate the effects of these 3

diabetic retinopathy

ACCORD Eye Study

Objectives

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Baseline (within 4 months of enrollment)

Sample size: n=4,065

4 years for all enrolled at baseline

ACCORD Eye Study

Eye Exam and Fundus Photos

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Clinical coordinator from the diabetes

Coordinating Center (Wake Forest U.) and

Eye exam form, fundus photographs sent to

clinic will schedule patient

ACCORD Eye Study

Study flow

Reading Center (U. of Wisconsin)

29Alexandria meeting

Feb 18-20, 2004