ACCORD: Action to Control CardiOvascular Risk in Diabetes

1
ACCORD Action to Control CardiOvascular Risk in
Diabetes

• Purpose
• To assess whether intensive therapy targeting
  normal glycated hemoglobin levels (lt6.0),
  compared with standard therapy targeting levels
  of 7.07.5, would reduce cardiovascular events
  in patients who have type 2 diabetes and either
  established cardiovascular disease or additional
  cardiovascular risk factors.
• Reference
• Gerstein HC, Miller ME, Byington RP, et al. for
  the Action to Control Cardiovascular Risk in
  Diabetes Study Group. Effects of intensive
  glucose lowering in type 2 diabetes. N Engl J Med
  200835825452559.

2
ACCORD Action to Control CardiOvascular Risk in
Diabetes - TRIAL DESIGN -

• Design
• Randomized, double 2x2 factorial, multicenter,
  North American trial.
• Patients
• 10,251 patients were recruited from 77 centers.
  Patients had type 2 diabetes mellitus, glycated
  hemoglobin levels of 7.5, and were either aged
  4079 years old and had cardiovascular disease or
  aged 5579 years old and had anatomical evidence
  of significant atherosclerosis, albuminuria, left
  ventricular hypertrophy, or more than two
  additional cardiovascular risk factors.
• Follow-up and primary endpoint
• Patients receiving intensive therapy were
  followed up every month for 4 months and then
  every 2 months in the standard-therapy group,
  patients had glycemic management visits every 4
  months. The primary endpoint was a composite of
  the first occurrence of non-fatal myocardial
  infarction, non-fatal stroke, and cardiovascular
  death.
• Treatment
• Comprehensive intensive therapy targeting a
  glycated hemoglobin level of lt6.0 or standard
  therapy targeting levels of 7.07.9.

3
ACCORD Action to Control CardiOvascular Risk in
Diabetes - TRIAL DESIGN continued -

Baseline characteristics
Intensive therapy
Standard therapy
(n5128)
(n5123)
Mean age (years)
62.2
62.2
Female sex ()
38.7
38.4
Previous cardiovascular event ()
35.6
34.8
Median duration of diabetes (years)
10
10
8.1
8.1
Median glycated hemoglobin ()
Current smoker ()
14.3
13.7
Systolic blood pressure (mm Hg)
136.2
136.5
Diastolic blood pressure (mm Hg)
74.8
75.0
Body mass index (kg/m2)
32.2
32.2
Gerstein et al. N Eng J Med 200835825452559.
4
ACCORD Action to Control CardiOvascular Risk in
Diabetes - RESULTS -

• At 1 year, median glycated hemoglobin levels
  stabilized at 6.4 in the intensive therapy group
  and at 7.5 in the standard therapy group.
• Primary endpoint
• There was a non-significant reduction in the
  rates of the primary endpoint in the intensive
  group versus the standard therapy group (6.9 vs.
  7.2, respectively hazard ratio HR 0.90
  p0.16).
• Secondary endpoints
• The rate of death from any cause was
  significantly higher with intensive therapy than
  it was with standard therapy (5.0 vs. 4.0,
  respectively HR 1.22 p0.04), as was the rate
  of death from cardiovascular causes (2.6 vs.
  1.8, respectively HR, 1.35 p0.004).
• Consequently, the intensive regimen was
  discontinued after 3.5 years, 17 months before
  the scheduled end of the study.
• Other resultsHypoglycemia requiring assistance,
  and weight gain of gt10 kg since baseline were
  significantly more common with intensive therapy
  than with standard therapy (16.2 vs. 5.1
  plt0.001 and 27.8 vs. 14.1 plt0.001,
  respectively).

5
ACCORD Action to Control CardiOvascular Risk in
Diabetes - RESULTS continued -
Kaplan-Meier curves for primary endpoint and
death from any cause
No. at risk Intensive therapy Standard therapy
Gerstein et al. N Eng J Med 200835825452559.
6
ACCORD Action to Control CardiOvascular Risk in
Diabetes - RESULTS continued -
Median glycated hemoglobin levels at each study
visit
No. at risk Standard therapy Intensive therapy
Gerstein et al. N Eng J Med 200835825452559.
7
ACCORD Action to Control CardiOvascular Risk in
Diabetes -SUMMARY-

• In patients with type 2 diabetes and either
  established cardiovascular disease or additional
  cardiovascular risk factors and a median glycated
  hemoglobin level of 8.1
• A strategy targeting glycated hemoglobin levels
  of lt6.0 increases the rate of death from any
  cause after an average of 3.5 years in comparison
  with a strategy targeting levels of 7.07.9
• The increase in mortality is equivalent to one
  extra death for every 95 patients who were
  treated for 3.5 years
• The harm caused by intensive therapy might be
  caused by either the approach used for rapidly
  lowering glycated hemoglobin levels or the levels
  that were achieved