William C Cushman MD FACP FAHA William C. Cushman, MD, FACP, FAHA Veterans Affairs Medical Center, Memphis, TN

For The ACCORD Study Group

ACCORD Double 2 x 2 Factorial DesignLipid BP

Placebo Fibrate Intensive Standard

IntensiveGlycemic

Placebo Fibrate Intensive Standard

GlycemicControl 51281383 1374 11931178

StandardGlycemicControl 512313911370 11781184Control 5123

237123622753 2765

1178

10 251237123622753 2765 10,251

4733*5518 47335518* 94% power for 20% reduction in event rate, assuming

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

ACCORD BP Trial Eligibilityg y

• Stable Type 2 Diabetes >3 months

• HbA1c 7.5% to 11% (or <9% if on more meds)• High CVD risk = clinical or subclinical disease or >2 risk factors

• Age (limited to <80 years after Vanguard)≥ 40 yrs with history of clinical CVD (secondary prevention)≥ 55 yrs otherwise

• Systolic blood pressure130 to 160 mm Hg (if on 0-3 meds)130 to 160 mm Hg (if on 0-3 meds)161 to 170 mm Hg (if on 0-2 meds)171 to 180 mm Hg (if on 0-1 meds)

• Urine protein <1.0 gm/24 hours or equivalent • Serum Creatinine <1.5 mg/dl

Many drugs/combinations provided to achieve goal BP according d i d i to randomized assignment.

Intensive Intervention:

◦ 2-drug therapy initiated: thiazide-type diuretic + ACEI, ARB, or β-blocker.

◦ Drugs added and/or titrated at each visit to achieve SBP <120 mm Hg.

◦ At periodic “milepost” visits: addition of another drug “required” if not at goal.

Standard Intervention:

◦ Intensify therapy if SBP >160 mm Hg @ 1 visit or >140 mm Hg @ 2 consecutive visits

◦ Down-titration if SBP <130 mm Hg @ 1 visit or <135 mm Hg @ 2 consecutive visits

Mean # MedsIntensive: 3.2 3.4 3.5 3.4

Standard: 1.9 2.1 2.2 2.3

A 133 5 St d d 119 3 I t i D lt 14 2Average : 133.5 Standard vs. 119.3 Intensive, Delta = 14.2

Intensive StandardIntensive Events (%/yr)

StandardEvents (%/yr) HR (95% CI) P

Primary 208 (1.87) 237 (2.09) 0.89 (0.73-1.07) 0.20

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

Cardiovascular 60 (0 52) 58 (0 49) 1 06 (0 74 1 52) 0 74Deaths

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 (0.41-0.97) 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 anginacomposite of the primary outcome, revascularization and unstable angina

(HR=0.95, p=0.40)

Primary Outcome by Pre-defined Subgroups

Also examined DBP tertiles (p=0.70) and number of screening meds (p=0.44)

The ACCORD BP Trial results provide no conclusive evidence The ACCORD BP Trial results provide no conclusive evidence that a strategy targeting normal SBP, compared with a standard SBP goal, reduces a composite of major CVD events g , p jin high-risk patients with type 2 diabetes, in the setting of good glycemic control.

◦ There was a higher risk of SAE in the intensive BP group, but also a 41% lower stroke rate.

◦ The stroke effect is consistent with other BP treatment trials.

◦ SBP goal <120 mm Hg may reduce strokes in patients with diabetes like those in ACCORDdiabetes like those in ACCORD.