Action to Control Cardiovascular Risk in Diabetes (ACCORD)
Condition: Atherosclerosis; Cardiovascular Diseases; Hypercholesterolemia; Hypertension; Diabetes Mellitus, Type 2; Diabetes Mellitus; Coronary Disease
MeSH terms: Cardiovascular Diseases; Atherosclerosis; Coronary Disease; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypercholesterolemia
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to prevent major cardiovascular events (heart attack, stroke, or
      cardiovascular death) in adults with type 2 diabetes mellitus using intensive glycemic
      control, intensive blood pressure control, and multiple lipid management.
    

Detailed description: 
      BACKGROUND:

      Currently, about 17 million Americans have been diagnosed with diabetes and more than 90
      percent of them have type 2 diabetes. The number of people with this form of diabetes,
      formerly known as adult onset or non-insulin dependent diabetes, is growing rapidly. By 2050,
      the number of Americans with diagnosed diabetes is projected to increase by 165 percent to 29
      million, of whom 27 million will have the type 2 form. Cardiovascular disease (CVD) is the
      leading cause of death in people with type 2 diabetes; these individuals die of CVD at rates
      two to four times higher than those who do not have diabetes. They also experience more
      nonfatal heart attacks and strokes.

      Type 2 diabetes is associated with older age and is more common in those who are overweight
      or obese and have a family history of diabetes. Women with a history of diabetes during
      pregnancy, adults with impaired glucose tolerance, people with a sedentary lifestyle, and
      members of a minority race/ethnicity are also at a greater risk for developing type 2
      diabetes. African Americans, Hispanic/Latino Americans, American Indians, and some Asian
      Americans and Pacific Islanders are at particularly high risk for type 2 diabetes.

      DESIGN NARRATIVE:

      The three strategies tested in ACCORD included the following: (1) Blood sugar - ACCORD was
      designed to determine whether lowering blood glucose to a level closer to normal than called
      for in current guidelines reduces CVD risk. The study estimated effects on CVD of that level
      compared with a level that is usually targeted. (2) Blood pressure - many people with type 2
      diabetes have high blood pressure. The blood pressure part of the trial was designed to
      determine the effects of lowering blood pressure in the context of good blood sugar control,
      that is to determine whether lowering blood pressure to normal (systolic pressure less than
      120 mm Hg) will better reduce CVD risk, as compared to a usually-targeted level in current
      clinical practice (i.e., below the definition of hypertension; systolic pressure less than
      140 mm Hg). (3) Blood Fats - Many people with diabetes have high levels of LDL ("bad")
      cholesterol and triglycerides, as well as low levels of HDL ("good") cholesterol. ACCORD
      participants who are selected for this part of the trial were assigned to an intervention to
      improve blood fat levels. This part of the study looked at the effects of lowering LDL
      cholesterol and blood triglycerides and increasing HDL cholesterol compared to an
      intervention that only lowers LDL cholesterol, all in the context of good blood sugar
      control. A drug from a class of drugs called "fibrates" was used to lower triglycerides and
      increase HDL cholesterol, whereas a drug from the class of drugs called "statins" was used to
      lower LDL cholesterol.

      All ACCORD participants received blood sugar treatment from the study. Based on the second
      trial (Blood Pressure or Lipid) they were assigned to, participants also received their high
      blood pressure or cholesterol care from the study. Study participants received all medication
      and treatments related to the study free of charge. Individuals who selected for and
      consented to participate in the ACCORD study continued to see their personal physician for
      all other health care.

      In summary, the ACCORD Study was a double 2x2 factorial design with factors consisting of:
      intensive versus standard glycemic control, intensive versus standard blood pressure control,
      and blinded fenofibrate or placebo in combination with simvastatin to maintain desirable
      LDL-C levels. All 10,251 participants were randomized to the glycemic interventions; a
      subgroup of 4,733 participants who met the blood pressure entry criteria were randomized to
      the blood pressure interventions in one 2x2 trial; and a distinct subgroup of 5,518
      participants who met the lipid entry criteria were randomized to the lipid interventions in
      the second 2x2 trial. All participants had established type 2 diabetes and were recruited
      from 77 clinical centers in the United States (64 sites) and Canada (13 sites).

      On February 6, 2008, the National Heart, Lung and Blood Institute (NHLBI) announced that
      participants in the intensive glycemia treatment would be transitioned to the ACCORD standard
      glycemic treatment approach due to higher mortality in the intensive treatment group
      terminating the experimental arm of the Glycemia Trial early. The Blood Pressure and Lipid
      trials continued as designed to their planned termination in 2009.
    

Intervention name(s): Anti-hyperglycemic Agents; Anti-hypertensive Agents; Blinded fenofibrate or placebo plus simvastatin
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals (intensive control <6%; standard control 7.0-7.9%).; Multiple anti-hypertensive agents as needed to reach Blood Pressure Trial arm-specific goals (intensive control <120 mm Hg; standard control <140 mm Hg).; Double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m2 or 54 mg/day in patients with eGFR <50 mL/min/1.73m2 or matching placebo in combination with open label simvastatin 20 - 40 mg/day.
Other intervention name(s): glimepiride (Amaryl); metformin (Glucophage); repaglinide (Gluconorm, Prandin); rosiglitazone (Avandia); pioglitazone (Actos); human regular insulin (Novolin ge Toronto); human NPH (Novolin N); human mixed (Novolin 70/30); human isophane (Novolin ge NPH); human 30/70 (Novolin ge 30/70); insulin aspart (NovoRapid, NovoLog); insulin detemir (Levemir); human regular insulin (Novolin R); insulin glargine (Lantus); Acarbose; benazepril (Lotensin, Zestril, Altace); chlorthalidone (Thalitone); metoprolol (Toprol XL); diltiazem (Tiazac); plendil (Felodipine); terazosin (Hytrin); candesartan (Atacand); valsartan (Diovan); furosemide; reserpine; hydralazine; carvedilol (Coreg); triamterene / hydrochlorothiazide (Dyazide); metoprolol / hydrochlorothiazide(Lopressor HCT); benazepril / hydrochlorothiazide (Lotensin HCT); lisinopril / hydrochlorothiazide (Zestoretic); candesartan / hydrochlorothiazide (Atacand HCT); valsartan / hydrochlorothiazide (Diovan HCT); amlodipine / benazepril (Lotrel); fenofibrate (Tricor)
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Metformin; Insulin Glargine; Pioglitazone; Insulin Aspart; Glimepiride; Rosiglitazone; Insulin Detemir; Acarbose; Repaglinide; Hypoglycemic Agents; Metoprolol; Felodipine; Amlodipine; Valsartan; Hydrochlorothiazide; Carvedilol; Candesartan; Candesartan cilexetil; Lisinopril; Chlorthalidone; Diltiazem; Benazepril; Hydralazine; Antihypertensive Agents; Reserpine; Hydrochlorothiazide, lisinopril drug combination; Hydrochlorothiazide-triamterene; Triamterene; Furosemide; Simvastatin; Fenofibrate; Terazosin
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Diabetes Mellitus, Non-Insulin-Dependent