ACCORD: Treatment Effect onAll-Cause Mortality

Patients with events

(%)

Time (years)

25

0

20

15

10

5

01 2 3 4 5 6

Standard therapy

Intensive therapyHR 1.22 (1.01-1.46)

P = 0.04

1.41%/yr

1.14%/yr

ACCORD Study Group. N Engl J Med 2008;358:2545–59.

VADT – Non Fatal CV Events

Hazard Ratio and CL

0.845 (0.704, 1.016) p=0.0725

Time to nonfatal outcome1.0

0.8

0.6

0.4

0.2

0.00 1 2 3 4 5 6 7

Follow-up time (years)

Prop

ortio

n fr

ee o

f non

fata

l out

com

e

VADT Study Group. N Engl J Med 2009; 360:129-139.

ADVANCE: Treatment Effect on Primary Macrovascular Outcome

CV death, MI stroke

Cumulative incidence (%)

Follow-up (months)

25

20

15

10

5

00 6 12 18 24 30 36 42 48 54 60 66

HR 0.94 (0.84-1.06)P = 0.32 Standard

control

Intensive control

ADVANCE Collaborative Group. N Engl J Med 2008;358:2560–72.

VADT: Effects of RecentSevere Hypoglycemia

• Predictor of CV death HR 4.04 p≤0.008

• Predictor of all cause mortalityStandard HR 5.89 p=0.001Intensive HR 1.28 p=0.68

VADT Study Group. N Engl J Med 2009; 360:129-139.

Lancet 373:1765-72, 2009

Baseline Characteristics of Participants and Study Design of Clinical Trials to Compare Intensive glucose-lowering versus Standard Treatment

Kay et al, Lancet 373:1765-72, 2009

Study Design of Clinical Trials to Compare Intensive glucose-lowering versus Standard Treatment

Kay et al, Lancet 373:1765-72, 2009

Event Rates of Cardiovascular Outcomes of Intensive-Lowering versus Standard Treatments

Kay et al, Lancet 373:1765-72, 2009

Probability of events of non-fatal myocardial infarction with intensive glucose-lowering vs. standard treatment

Ray et al, Lancet 2009; 373: 1765–72

Probability of events of coronary heart disease with intensive glucose-lowering vs. standard treatment

Probability of events of stroke with intensive glucose-lowering versus standard treatment

Ray et al, Lancet 2009; 373: 1765–72

Probability of events of all-cause mortality with intensive glucose-lowering versus standard treatment

Ray et al, Lancet 2009; 373: 1765–72

Annals Internal Medicine 2009; 151: 394-403

Pooled relative risk and risk differences (per 1000 patients over 5 years of treatment) estimates of nonfatal MI, fatal MI, nonfatal stroke, fatal stroke, and PAD

UKPDS 34

UKPDS 34

ACCORD

ADVANCE

VADT

Kelly et al, Ann Inter Med 2009; 151: 394-403

Pooled relative risk and risk differences (per 1000 patients over 5 years of treatment) estimates of nonfatal MI, fatal MI, nonfatal stroke, fatal stroke, and PAD

Kelly et al, Ann Inter Med 2009; 151: 394-403

Pooled relative risk and risk differences (per 1000 patients over 5 years of treatment) estimates of severe hypoglycemia

Kelly et al, Ann Inter Med 2009; 151: 394-403

Summary of Meta-Analysis• These 2 meta-analysis found that, compared with

conventional control, intensive glucose control reduce the risk for cardiovascular disease (mostly nonfatal myocardial infarction) but not for cardiovascular death or all-cause mortality, and increased risk for severe hypoglycemia.

• Early trials suggested possible decreased risk for death with intensive control, whereas some more recent trials suggested possible increased risk for death with more stringent control.