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CVD Risk Factor Management in Diabetic Patients: What's New in 2010?. The ACCORD TrialThe trial with 3 arms but no legs to stand on... Other Recent Negative Prevention Trials in Diabetes

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Mayo Clinic Outpatient Center

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CVD Risk Factor Management in

Diabetic Patients:

What's New in 2010?

Thomas G Allison, PhD, MPHCardiovascular Diseases and Internal Medicine

Mayo ClinicRochester, MN

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• Disclosures: none

• Off-label use of drugs: none

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The ACCORD Trial

The trial with 3 arms but no legs to stand on

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ACCORD Double 2 x 2 Factorial Design

1391 1370

1193

1178 1184

1178

10,251

5518

* 94% power for 20% reduction in event rate, assuming

standard group rate of 4% / yr and 5.6 yrs follow-up

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ACCORD Baseline Patient

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ACCORD-Glucose Treatment

Approach

HbA1c Target: < 6.0% versus < 7.0-7.9%

Duration of follow-up: Median 3.4 yrs

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ACCORD Glucose control

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ACCORD Primary outcome

(CV death, MI, stroke)

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ACCORD All-cause mortality

ACCORD Study Group N Engl J Med.008;358:2545-59.

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ACCORD-Blood Pressure

• N=4733 type 2 diabetics

• Systolic blood pressure goals

– < 120 mmHg versus < 140 mmHg

• Primary outcome (composite):

– Nonfatal MI / stroke / CV death

• Mean follow-up: 4.7 years

• Many drugs/combinations provided to achieve goal BP according to randomized assignment

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Average after 1 st year: 133.5 Standard vs 119.3 Intensive, Delta = 14.2

Mean # Meds

Intensive: 3.2 3.4 3.5 3.4

Standard: 1.9 2.1 2.2 2.3

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Primary and Secondary Outcomes

Intensive Events (%/yr)

Standard Events (%/yr) HR (95% CI) p

Primary 208 (1.87) 237 (2.09) 0.88 (0.73-1.06) 0.20

Total Mortality 150 (1.28) 144 (1.19) 1.07 (0.85-1.35) 0.55

Cardiovascular

Deaths 60 (0.52) 58 (0.49) 1.06 (0.74-1.52) 0.74Nonfatal MI 126 (1.13) 146 (1.28) 0.87 (0.68-1.10) 0.25

Nonfatal Stroke 34 (0.30) 55 (0.47) 0.63 (0.41-0.96) 0.03

Total Stroke 36 (0.32) 62 (0.53) 0.59 (0.39-0.89) 0.01

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• N=5518 type 2 diabetics

• Open label Simvastatin + PBO or fenofibrate

• Primary outcome (composite):

– Nonfatal MI / stroke / CV death

• Mean follow-up: 4.7 years

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Other Recent Negative Prevention Trials

in Diabetes

Lipid Treatment

• FIELD

– No benefit to Fenofibrate versus PBO

Blood Pressure Treatment

• INVEST

– No difference in outcomes with SBP < 130

versus 130-140 mmHg in type 2 diabetics

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Perspective on ACCORD

• Was it a poorly designed or conducted trial?

• Or does it simply fit in with other recent

negative CV prevention trials?

– Mostly add-on or titration trials

– Background medical therapy is better than in older positive trials

– More intensive intervention comes with costs

• We nearing the limits of office-based CV prevention with drug treatment of

conventional CV risk factors Lower is not always better and comes at a cost.

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Management of CAD in Type 2

Diabetes

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5-Year Outcomes: BARI-2D Trial

0 20 40 60 80 100

Survival, Revascularization vs Medical Therapy

Revascularization Medical therapy

P=0.97

0 20 40 60 80 100

Revascularization Medical therapy

P=0.70

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BARI 2-D: PCI versus Medical

Similar Results to COURAGE Trial

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BARI 2-D: CABG versus Medical

Consistent with SYNTAX Trial

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Insulin Sensitization versus Insulin

Provision: BARI 2-D

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• PCI provides no additional benefit to optimal medical therapy as an initial treatment strategy in Type 2 diabetics– Similar results to COURAGE Study 2007

• Type 2 diabetics with severe CAD will show benefit with CABG

• Optimal control of CV risk factors is indicated for all Type 2 diabetics

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