1. ACCORD Design and Baseline Characteristics
Presented at the American Diabetes Association
68th Scientific Sessions on June 10, 2008.

2. ACCORD Trial Overall Goal
To determine whether CVD event rates can be reduced in people with diabetes by intensively targeting three important CVD risk factors: hyperglycemia, dyslipidemia, and high blood pressure.
Three trials in one research program
Double 2 by 2 factorial design

3. Glycemia Trial Research Question
In middle aged/older people with type 2 DM at high risk for a CVD event, does a therapeutic strategy that targets an A1C < 6.0% reduce CVD event rates more than a strategy that targets an A1C between 7.0% & 7.9% (with the expectation of achieving a median level of 7.5%)?

4. Glycemia Trial Rationale
Observational studies supportive
Each 1% higher A1C associated with 18% greater risk of CVD1
CVD-glucose relationship extends into the normal range
Clinical trials inconclusive2
Study
Mean A1C (Intense)
Mean A1C (Control)
Relative Risk Reduction for CVD (95% CI)
UKPDS (I/SU)
7.0%
7.9%
16% (0,29)
UKPDS (Met)
7.4%
8.0%
39% (11,59)
Kumamoto
7.1%
9.4%
46% (NS)
VACSDM
9.3%
-56% (-170,10)
DIGAMI
29% (4,51)
UGDP(IVAR)
FPG
mg/dL
mg/dL
9% (NS)
1. Selvin E, et al. Ann Intern Med. 2004;141:
2. Goff DC Jr, et al. Am J Cardiol. 2007;99[suppl]:4i-20i.

5. ACCORD Design
Multi-center, randomized, controlled, double 2x2 factorial
Glycemia and BP Trials Open Label with Blinded Endpoint Assessment
Lipid Trial placebo controlled
Glycemia Trial
89% power to detect a 15% difference in major CVD events between treatment groups.
Assumed at least 1% difference in A1C needed
Goal A1C difference 1.5%
Expected primary event rate about 3% per year
Sample size goal 10,000
77 clinics in US and Canada

6. Double 2 X 2 Factorial DesignBP
Lipid
Intensive
(SBP<120)
Standard
(SBP<140)
Statin + Masked Study Drug
Statin + Masked Study Drug
Intensive
Glycemia
(A1C<6%)
1178
1193
1383
1374
5128*
Standard
Glycemia
(A1C 7-7.9%)
1184
1178
1370
1391
5123*
2362*
2371*
2753*
2765*
10,251
*Primary analyses compare the marginals for main effects

7. Participant Eligibility
Stable Type 2 Diabetes for 3+ months
A1C >7.5% AND <9% (more meds) OR <11% (fewer meds)
Age previous CVD events OR
Age with:
anatomical ASCVD, albuminuria, LVH OR
> 2 CVD risk factors (dyslipidemia, hypertension, smoking, obesity)
BMI < 45; Cr < 1.5 (133 uM)
No frequent/recent serious hypoglycemia
Able/willing to take insulin, do glucose monitoring
Eligible for BP or Lipid Trial

8. ACCORD Outcomes Primary: Secondary/Other:
First occurrence of nonfatal MI OR Nonfatal Stroke OR CV Death
Secondary/Other:
Each component of 10
Expanded CVD: Revasc & HF Hosp
Total mortality
Microvascular (nephropathy, neuropathy, eye)
Eye photo substudy (N = 3537)
HRQL (N = 2053); Cost (N = 4311)
MIND: cognition, brain volume (MRI)
Falls/Fractures/BMD

9. Treatment Strategies
Compared with the standard group, the intensive group had:
Lower A1C goal (< 6% vs %)
More visits (q 1-2 mo + at least 1 interim call vs. q 4 mo)
Point of care A1C
Greater use of multiple medications
Greater use of insulin

10. Baseline Characteristics
Intensive
(N = 5128)
Standard
(N = 5123)
Age
62.2
Women
38.7
38.4
Median DM Duration 10
Previous CVD Event
35.6
34.8
White/Black
64.4/19.7
64.5/18.9
Current Smoker
14.3
13.7
Mean BMI
32.2
Mean SBP/DBP
136.2/74.8
136.5/75.0
Mean/Median A1C
8.3 / 8.1
Mean FG
175
176
Mean LDL / HDL
105 / 47

11. Baseline Medications Insulin (%) 34.1 35.7 Metformin (%) 59.7 60.0
Intensive
(N = 5128)
Standard
(N = 5123)
Insulin (%)
34.1
35.7
Metformin (%)
59.7
60.0
Sulfonylurea (%)
50.8
49.4
TZD (%)
19.5
19.2
BP Drug (%)
84.9
86.0
ACE-I (%)
53.0
ASA (%)
54.8
54.1
Beta Blocker (%)
28.7
29.9
Thiazide (%)
26.5
26.4
Statin (%)
61.7
62.4

12. Last Clinical Measure Intensive Standard P Last LDL 90.8 ± 33.5
Intensive
Standard P
Last LDL
90.8 ± 33.5
90.6 ± 34.0
0.74
SBP
126.4 ± 16.7
127.4 ± 17.2
0.002
DBP
66.9 ± 10.5
67.7 ± 10.6
<0.001
BP Drug (%)
91.0
92.0
0.06
ACE-I (%)
69.7
71.9
0.02
ASA (%)
75.5
0.98
Beta Blocker (%)
47.5
48.6
0.27

13. ACCORD Trial Design Summary
Large complex research program
Multi-center, randomized, controlled factorial trials of 3 approaches to reduce CVD in T2DM
Glycemia Trial Open Label with Blinded Endpoint Assessment
Interventions designed to produce 1-1.5% difference in A1C
Goals: A1C < 6% vs 7 – 7.9%
Primary endpoint: major CVD events
Participants: diverse group of middle-aged and older adults with established T2DM with or at high risk for CVD
High use of evidence-based background therapies: ASA, ACE-I, BB, Statins
Results should be interpreted in context of population studied and other therapies received.