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William C. Cushman, MD, FACP, FAHAVeterans Affairs Medical Center, Memphis,TN
For The ACCORD Study Group
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Dr. Cushman reports receiving
Consulting Fees from Novartis, Takeda, Sanofi-Aventis, Bristol-Myers Squibb, King, Daichi-Sankyo, Gilead, Theravance, Pharmocopeia, andSciele
Grant Support from Novartis, GlaxoSmithKline andMerck
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ACCORD Sponsor, Collaborators
and Contributors
Collaboration & support
National Institute of Diabetes
& Digestive & Kidney
Diseases (NIDDK)
National Eye Institute (NEI) National Institute on Aging
(NIA)
Centers for Disease Control
and Prevention (CDC)
Sponsor: The National Heart, Lung, and Blood Institute (NHLBI)
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ACCORD Study Design
Randomized multi-center clinical trial
Conducted in 77 clinical sites in North America
(U.S. and Canada)
Designed to independently test three medical
strategies to reduce CVD in diabetic patients
BP question: does a therapeutic strategy
targeting systolic blood pressure (SBP)
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ACCORD Double 2 x 2 Factorial Design
Intensive
Glycemic
Control 5128
Standard
Glycemic
Control 5123
Lipid BP
Placebo Fibrate Intensive Standard
237123622753 2765
1383 1374
13911370
1193
11781184
1178
10,251
4733*5518*
94% power for 20% reduction in event rate, assumingstandard group rate of 4% / yr and 5.6 yrs follow-up
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ACCORD BP Trial Eligibility
Stable Type 2 Diabetes >3 months
HbA1c 7.5% to 11% (or
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Many drugs/combinations provided to achieve goal
BP according to randomized assignment. Intensive Intervention:
2-drug therapy initiated: thiazide-type diuretic + ACEI, ARB,or -blocker.
Drugs added and/or titrated at each visit to achieve SBP
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Characteristic Mean or % Characteristic Mean or %
Age (yrs) 62 Blood Pressure (mmHg)
139/76
Women % 48 On Antihypertensive%
87
2 prevention % 34 Creatinine (mg/dL) 0.9
Race / Ethnicity eGFR(mL/min/1.73m2)
92
White % 61 DM Duration (yrs)* 10
Black % 24 A1C (%) 8.3
Hispanic % 7 BMI (kg/m2) 32
*Median value
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Average after 1st 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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IntensiveN (%)
StandardN (%)
P
Serious AE 77 (3.3) 30 (1.3)
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Intensive Standard P
Potassium(mean mg/dl)
4.3 4.4 0.17
Serum Creatinine(mean mg/dl)
1.1 1.0
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IntensiveEvents(%/yr)
StandardEvents(%/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
CardiovascularDeaths
60 (0.52) 58 (0.49) 1.06 (0.74-1.52) 0.74
Nonfatal 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
Also examined Fatal/Nonfatal HF (HR=0.94, p=0.67), a composite of fatal
coronary events, nonfatal MI and unstable angina (HR=0.94, p=0.50) and a
composite of the primary outcome, revascularization and unstable angina
(HR=0.95, p=0.40)
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Pa
tientswithEvents(%
)
0
5
10
15
20
Years Post-Randomization
0 1 2 3 4 5 6 7 8
Pa
tientswithEvents(%)
0
5
10
15
20
Years Post-Randomization
0 1 2 3 4 5 6 7 8
Nonfatal Stroke Total Stroke
HR = 0.63
95% CI (0.41-0.96)HR = 0.59
95% CI (0.39-0.89)
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Intensive BP management reduced the rate of twoclosely correlated secondary end points: totalstroke (p=0.01) and nonfatal stroke (p=0.03).
Assuming that this finding was real, the numberneeded to treat to the lower SBP level to prevent
one stroke over 5 years was 89.These effects would be consistent with meta-
analyses summarizing the impact of a 10 mm Hgreduction in SBP on strokes from observational
studies (relative risk=0.64) and drug treatmenttrials (relative risk=0.59).
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rimary Outcome by Pre-defined Subgroups
Also examined DBP tertiles (p=0.70) and number
of screening meds (p=0.44)
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The ACCORD BP trial evaluated the effectof targeting a SBP goal of 120 mm Hg,compared to a goal of 140 mm Hg, inpatients with type 2 diabetes at increasedcardiovascular risk.
The results provide no conclusive
evidence that the intensive BP controlstrategy reduces the rate of a compositeof major CVD events in such patients.
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Published online March 14, 2010
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Mean # Meds
Intensive: 3.2 3.4 3.5 3.4
Standard: 1.9 2.1 2.2 2.3
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PatientswithEvents(%
)
0
5
10
15
20
Years Post-Randomization
0 1 2 3 4 5 6 7 8
PatientswithEvents(%
)
0
5
10
15
20
Years Post-Randomization
0 1 2 3 4 5 6 7 8
Primary OutcomeNonfatal MI, Nonfatal Stroke or CVD Death Total Stroke
HR = 0.8895% CI (0.73-1.06)
HR = 0.59
95% CI (0.39-0.89)
NNT for 5 years = 89
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PatientswithEvents(%
)
0
5
10
15
20
Years Post-Randomization
0 1 2 3 4 5 6 7 8
Primary OutcomeNonfatal MI, Nonfatal Stroke or CVD Death
HR = 0.8895% CI (0.73-1.06)
PatientswithEvents(%
)
0
5
10
15
20
Years Post-Randomization
0 1 2 3 4 5 6 7 8
Nonfatal Stroke
HR = 0.63
95% CI (0.41-0.96)
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PatientswithEvents(%
)
0
5
10
15
20
Years Post-Randomization
0 1 2 3 4 5 6 7 8
PatientswithEvents(%
)
0
5
10
15
20
Years Post-Randomization
0 1 2 3 4 5 6 7 8
Primary OutcomeNonfatal MI, Nonfatal Stroke or CVD Death Total Mortality
HR = 0.8895% CI (0.73-1.06)
HR = 1.07
95% CI (0.85-1.35)
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Pa
tientswithEvents(%
)
0
5
10
15
20
Years Post-Randomization
0 1 2 3 4 5 6 7 8
PatientswithEvents(%
)
0
5
10
15
20
Years Post-Randomization
0 1 2 3 4 5 6 7 8
Non Fatal MI CVD Deaths
HR = 0.8795% CI (0.68-1.10)
HR = 1.06
95% CI (0.74-1.52)