Action to Control Cardiovascular Risk in Diabetes (ACCORD trial)

Introduction

Study characteristics:

• 10,251 adults with type 2 diabetes at high risk for cardiovascular disease
• ACCORD lipid study:
  • 5000 diabetics with hemoglobin A1c >= 7.5%
  • mean age 62 years
• ACCORD blood pressure study:
  • 4733 diabetics, mean age 62 years, 48% women
  • hemoglobin A1c >= 7.5%
  • systolic blood pressure 130-180 mm Hg
  • on <= 3 antihypertensive agents
  • no proteinuria

Treatment groups:

• glycemic control two strategies:
  • treatment to intensively lower blood glucose below 6.0%
  • standard treatment
• lipid study:
  • fenofibrate 160 mg QD vs placebo
  • all participants received simvastatin
• ACCORD blood pressure study
  • systolic blood pressure target < 120 mm Hg, vs
  • systolic blood pressure target < 140 mm Hg (standard therapy for non diabeitcs)
  • mean follow-up 4.7 years
  • lower BP in the intensive-care group was achieved by prescribing more drugs in every antihypertensive class

Results:

• glycemic control:
  • intensive treatment arm ended early because of more deaths in that group 257 vs 203 of an excess of 3/1000/year
  • reasons for this are unclear
  • no particular pharmaceutical agent was implicated
  • no benefit for intensive glucose control in patients with long-standing diabetes mellitus type 2
  • fewer non-fatal acute coronary events despite higher cardiovascular & all-cause mortality
• lipid study
  • mean LDL cholesterol dropped 20 mg/dL (both groups)
  • mean HDL cholesterol increased 3.2 mg/dL (fenofibrate) vs 1.5 mg/dL (placebo)
  • median serum triglycerides decreased 41 mg/dL (fenofibrate) vs 17 mg/dL (placebo)
  • adverse cardiovascular events similar in 2 lipid groups 2.2% vs 2.4%
  • more adverse effects in women assigned to fenofibrate group
  • fenofibrate group was significantly more likely to leave study because of a decrease in glomerular filtration rate (GFR) 2.4% vs 1.1%
• ACCORD blood pressure study
  • mean number of antihypertensive agents at 1 year was 3.1 in the intensive care group vs 2.1 in the standard care group
  • no difference in cardiovascular mortality
    • annual rates of all-cause mortality was hight in the intensive care group 1.28% vs 1.19% in the standard care group
  • adverse cardiovascular events was 1.9% in the intensive care group vs 2.1% in the standard care group, a non-significant difference
  • stroke was significantly lower in the intensive care group 0.32% vs 0.53%
  • serious adverse effects were significantly higher in the intensive care group
    • 3.3% vs 1.3% attributed to antihypertensive agents
    • more decrements in renal function
    • more episodes of syncope, bradycardia, hyperkalemia, hypotension
• intensive blood pressure control does not slow progression of retinopathy in diabetics
• microvascular outcomes
  • intensive glycemic control did NOT slow
    • end-stage renal disease
    • rise of serum creatinine to >3.3 mg/dL, or
    • need for photocoagulation or vitrectomy to treat retinopathy
• ACCORD retinopathy study
  • combination of intense glycemic control plus lipid control appeared to reduce progression of retinopathy, but editorialist notes findings not straightfoward

Notes

• increased mortality associated with intensive glycemic control trumps any benefit in reduction of microvascular complications

More general terms

• clinical trial

Additional terms

• ADVANCE trial
• diabetes mellitus type 2 (insulin-resistant)