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Action to Control Cardiovascular Risk in Diabetes (ACCORD) (ACCORD)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00000620
First Posted: October 28, 1999
Last Update Posted: November 22, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute on Aging (NIA)
National Eye Institute (NEI)
Centers for Disease Control and Prevention
Information provided by (Responsible Party):
National Heart, Lung, and Blood Institute (NHLBI)
  Purpose
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.

Condition Intervention Phase
Atherosclerosis Cardiovascular Diseases Hypercholesterolemia Hypertension Diabetes Mellitus, Type 2 Diabetes Mellitus Coronary Disease Drug: Anti-hyperglycemic Agents Drug: Anti-hypertensive Agents Drug: Blinded fenofibrate or placebo plus simvastatin Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Action to Control Cardiovascular Risk in Diabetes (ACCORD)

Resource links provided by NLM:


Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:
  • First Occurrence of a Major Cardiovascular Event (MCE); Specifically Nonfatal Heart Attack, Nonfatal Stroke, or Cardiovascular Death (Measured Throughout the Study) in the Glycemia Trial. [ Time Frame: 4.9 years ]

    Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. This was the primary outcome measure in all three trials: Glycemia (all participants), Blood Pressure (subgroup of participants not in Lipid Trial), and Lipid (subgroup of participants not in Blood Pressure Trial).

    In the Glycemia Trial, a finding of higher mortality in the intensive arm group led to an early discontinuation of therapy after a mean of 3.5 years of follow-up. Intensive arm participants were transitioned to standard arm strategy over a period of 0.2 year and followed for an additional 1.2 years to the planned end of the Glycemia Trial while participating in one of the other sub-trials (BP or Lipid) to their planned completion.


  • First Occurrence of Major Cardiovascular Event (MCE) in the Blood Pressure Trial. [ Time Frame: 4.7 years ]
    Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Primary outcome for Blood Pressure Trial.

  • First Occurrence of Major Cardiovascular Event (MCE) in the Lipid Trial. [ Time Frame: 4.7 years ]
    Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death in Lipid Trial participants.


Secondary Outcome Measures:
  • Death From Any Cause in the Glycemia Trial. [ Time Frame: 4.9 years ]

    Time to death from any cause. Secondary measure for Glycemia Trial.

    A finding of higher mortality in the intensive-therapy group led to an early discontinuation of therapy after a mean of 3.5 years of follow-up. Intensive arm participants were transitioned to standard arm strategy over a period of 0.2 year and followed for an additional 1.2 years to the planned end of the Glycemia Trial while participating in one of the other sub-trials (BP or Lipid).


  • Stroke in the Blood Pressure Trial. [ Time Frame: 4.7 years ]
    Time to first occurrence of nonfatal or fatal stroke among participants in the BP Trial.

  • First Occurrence of MCE or Revascularization or Hospitalization for Congestive Heart Failure (CHF) in Lipid Trial. [ Time Frame: 4.7 years ]
    Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, cardiovascular death, revascularization procedure or hospitalization for CHF in Lipid Trial participants.


Enrollment: 10251
Study Start Date: September 1999
Study Completion Date: December 2012
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Glycemia Trial: intensive control
Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels <6.0%.
Drug: Anti-hyperglycemic Agents
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%).
Other Names:
  • 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
Active Comparator: Glycemia Trial: standard control
Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels of 7.0 - 7.9%.
Drug: Anti-hyperglycemic Agents
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%).
Other Names:
  • 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
Experimental: BP Trial: intensive control
Open label administration of anti-hypertensive agents to reduce and maintain systolic blood pressure (SBP) level to <120 mmHg.
Drug: Anti-hypertensive Agents
Multiple anti-hypertensive agents as needed to reach Blood Pressure Trial arm-specific goals (intensive control <120 mm Hg; standard control <140 mm Hg).
Other Names:
  • 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)
Active Comparator: BP Trial: standard control
Open label administration of multiple anti-hypertensive agents to maintain SBP level <140 mm Hg.
Drug: Anti-hypertensive Agents
Multiple anti-hypertensive agents as needed to reach Blood Pressure Trial arm-specific goals (intensive control <120 mm Hg; standard control <140 mm Hg).
Other Names:
  • 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)
Experimental: Lipid Trial: fenofibrate
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 in combination with open label simvastatin.
Drug: Blinded fenofibrate or placebo plus simvastatin
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 Name: fenofibrate (Tricor)
Placebo Comparator: Lipid Trial: placebo
Double blind administration of placebo matching either 160 mg/day in participants with eGFR ≥50 mL/min/1.73m2 or 54 mg/day in participants with eGFR <50 mL/min/1.73m2 in combination with open label simvastatin.
Drug: Blinded fenofibrate or placebo plus simvastatin
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 Name: fenofibrate (Tricor)

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   40 Years to 79 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosed with type 2 diabetes mellitus, as determined by the new American Diabetes Association guidelines, which include a fasting plasma glucose level greater than 126 mg/dl (7.0 mmol/l), or a 2-hour postload value in the oral glucose tolerance test of greater than 200 mg/dl, with confirmation by a retest
  • For participants aged 40 years or older, history of CVD (heart attack, stroke, history of coronary revascularization, history of peripheral or carotid revascularization, or demonstrated angina)
  • For participants aged 55 years or older, a history of CVD is not required, but participant must be considered to be at high risk for experiencing a CVD event due to existing CVD, subclinical disease, or 2+ CVD risk factors
  • HbA1c 7.5%-9% (if on more drugs) or 7.5%-11% (if on fewer drugs)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00000620


Locations
United States, Minnesota
Minneapolis Medical Research Foundation
Minneapolis, Minnesota, United States, 55404
United States, New York
Columbia University
New York, New York, United States, 10027
United States, North Carolina
Wake Forest University
Winston-Salem, North Carolina, United States, 27106
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
United States, Tennessee
Veterans Affairs
Memphis, Tennessee, United States, 38104
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Canada, Ontario
McMaster University
Hamilton, Ontario, Canada
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute on Aging (NIA)
National Eye Institute (NEI)
Centers for Disease Control and Prevention
Investigators
Study Director: Denise Simons-Morton, MD, PhD National Heart, Lung, and Blood Institute (NHLBI)
Study Chair: William Friedewald, MD Columbia University, New York, NY
Principal Investigator: Robert Byington, PhD Wake Forest University, Winston-Salem, NC
  More Information

Additional Information:
Publications:
Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008 Jun 12;358(24):2545-59. doi: 10.1056/NEJMoa0802743. Epub 2008 Jun 6.
Cushman WC, Grimm RH Jr, Cutler JA, Evans GW, Capes S, Corson MA, Sadler LS, Alderman MH, Peterson K, Bertoni A, Basile JN; ACCORD Study Group. Rationale and design for the blood pressure intervention of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 2007 Jun 18;99(12A):44i-55i. Epub 2007 Apr 16.
Williamson JD, Miller ME, Bryan RN, Lazar RM, Coker LH, Johnson J, Cukierman T, Horowitz KR, Murray A, Launer LJ; ACCORD Study Group. The Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes Study (ACCORD-MIND): rationale, design, and methods. Am J Cardiol. 2007 Jun 18;99(12A):112i-122i. Epub 2007 Apr 12.
Sullivan MD, Anderson RT, Aron D, Atkinson HH, Bastien A, Chen GJ, Feeney P, Gafni A, Hwang W, Katz LA, Narayan KM, Nwachuku C, O'Connor PJ, Zhang P; ACCORD Study Group. Health-related quality of life and cost-effectiveness components of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: rationale and design. Am J Cardiol. 2007 Jun 18;99(12A):90i-102i. Epub 2007 Apr 13.
Bonds DE, Kurashige EM, Bergenstal R, Brillon D, Domanski M, Felicetta JV, Fonseca VA, Hall K, Hramiak I, Miller ME, Osei K, Simons-Morton DG; ACCORD Study Group. Severe hypoglycemia monitoring and risk management procedures in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 2007 Jun 18;99(12A):80i-89i. Epub 2007 Apr 17.
Kingry C, Bastien A, Booth G, Geraci TS, Kirpach BR, Lovato LC, Margolis KL, Rosenberg Y, Sperl-Hillen JM, Vargo L, Williamson JD, Probstfield JL; ACCORD Study Group. Recruitment strategies in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 2007 Jun 18;99(12A):68i-79i. Epub 2007 Apr 12.
Ginsberg HN, Bonds DE, Lovato LC, Crouse JR, Elam MB, Linz PE, O'connor PJ, Leiter LA, Weiss D, Lipkin E, Fleg JL; ACCORD Study Group. Evolution of the lipid trial protocol of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 2007 Jun 18;99(12A):56i-67i. Epub 2007 Apr 12.
Goff DC Jr, Gerstein HC, Ginsberg HN, Cushman WC, Margolis KL, Byington RP, Buse JB, Genuth S, Probstfield JL, Simons-Morton DG; ACCORD Study Group. Prevention of cardiovascular disease in persons with type 2 diabetes mellitus: current knowledge and rationale for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 2007 Jun 18;99(12A):4i-20i. Epub 2007 Apr 12. Review.
Gerstein HC, Riddle MC, Kendall DM, Cohen RM, Goland R, Feinglos MN, Kirk JK, Hamilton BP, Ismail-Beigi F, Feeney P; ACCORD Study Group. Glycemia treatment strategies in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 2007 Jun 18;99(12A):34i-43i. Epub 2007 Apr 19.
ACCORD Study Group, Buse JB, Bigger JT, Byington RP, Cooper LS, Cushman WC, Friedewald WT, Genuth S, Gerstein HC, Ginsberg HN, Goff DC Jr, Grimm RH Jr, Margolis KL, Probstfield JL, Simons-Morton DG, Sullivan MD. Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods. Am J Cardiol. 2007 Jun 18;99(12A):21i-33i. Epub 2007 Apr 16.
Chew EY, Ambrosius WT, Howard LT, Greven CM, Johnson S, Danis RP, Davis MD, Genuth S, Domanski M; ACCORD Study Group. Rationale, design, and methods of the Action to Control Cardiovascular Risk in Diabetes Eye Study (ACCORD-EYE). Am J Cardiol. 2007 Jun 18;99(12A):103i-111i. Epub 2007 Apr 13.

Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: ACCORD
NHLBI provides controlled access to IPD through BioLINCC. Access requires registration, evidence of local IRB approval or certification of exemption from IRB review, and completion of a data use agreement.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Chen LY, Bigger JT, Hickey KT, Chen H, Lopez-Jimenez C, Banerji MA, Evans G, Fleg JL, Papademetriou V, Thomas A, Woo V, Seaquist ER, Soliman EZ. Effect of Intensive Blood Pressure Lowering on Incident Atrial Fibrillation and P-Wave Indices in the ACCORD Blood Pressure Trial. Am J Hypertens. 2015 Oct 16. pii: hpv172. [Epub ahead of print]
Siraj ES, Rubin DJ, Riddle MC, Miller ME, Hsu FC, Ismail-Beigi F, Chen SH, Ambrosius WT, Thomas A, Bestermann W, Buse JB, Genuth S, Joyce C, Kovacs CS, O'Connor PJ, Sigal RJ, Solomon S; ACCORD Investigators. Insulin Dose and Cardiovascular Mortality in the ACCORD Trial. Diabetes Care. 2015 Nov;38(11):2000-8. doi: 10.2337/dc15-0598. Epub 2015 Oct 13.
Soliman EZ, Byington RP, Bigger JT, Evans G, Okin PM, Goff DC Jr, Chen H. Effect of Intensive Blood Pressure Lowering on Left Ventricular Hypertrophy in Patients With Diabetes Mellitus: Action to Control Cardiovascular Risk in Diabetes Blood Pressure Trial. Hypertension. 2015 Dec;66(6):1123-9. doi: 10.1161/HYPERTENSIONAHA.115.06236. Epub 2015 Oct 12.
Chow LS, Chen H, Miller ME, Marcovina SM, Seaquist ER. Biomarkers associated with severe hypoglycaemia and death in ACCORD. Diabet Med. 2016 Aug;33(8):1076-83. doi: 10.1111/dme.12883. Epub 2015 Sep 6.
Hempe JM, Liu S, Myers L, McCarter RJ, Buse JB, Fonseca V. The hemoglobin glycation index identifies subpopulations with harms or benefits from intensive treatment in the ACCORD trial. Diabetes Care. 2015 Jun;38(6):1067-74. doi: 10.2337/dc14-1844. Epub 2015 Apr 17.
Espeland MA, Probstfield J, Hire D, Redmon JB, Evans GW, Coday M, Lewis CE, Johnson KC, Wilmoth S, Bahnson J, Dulin MF, Green JB, Knowler WC, Kitabchi A, Murillo AL, Osei K, Rehman SU, Cushman WC; Look AHEAD Research Group; ACCORD Study Group. Systolic Blood Pressure Control Among Individuals With Type 2 Diabetes: A Comparative Effectiveness Analysis of Three Interventions. Am J Hypertens. 2015 Aug;28(8):995-1009. doi: 10.1093/ajh/hpu292. Epub 2015 Feb 9.
Chow LS, Chen H, Miller ME, Marcovina SM, Seaquist ER. Biomarkers related to severe hypoglycaemia and lack of good glycaemic control in ACCORD. Diabetologia. 2015 Jun;58(6):1160-6. doi: 10.1007/s00125-015-3512-0. Epub 2015 Feb 5.
Papademetriou V, Lovato L, Doumas M, Nylen E, Mottl A, Cohen RM, Applegate WB, Puntakee Z, Yale JF, Cushman WC; ACCORD Study Group. Chronic kidney disease and intensive glycemic control increase cardiovascular risk in patients with type 2 diabetes. Kidney Int. 2015 Mar;87(3):649-59. doi: 10.1038/ki.2014.296. Epub 2014 Sep 17.
Hugenschmidt CE, Lovato JF, Ambrosius WT, Bryan RN, Gerstein HC, Horowitz KR, Launer LJ, Lazar RM, Murray AM, Chew EY, Danis RP, Williamson JD, Miller ME, Ding J. The cross-sectional and longitudinal associations of diabetic retinopathy with cognitive function and brain MRI findings: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Diabetes Care. 2014 Dec;37(12):3244-52. doi: 10.2337/dc14-0502. Epub 2014 Sep 5.
Chew EY, Davis MD, Danis RP, Lovato JF, Perdue LH, Greven C, Genuth S, Goff DC, Leiter LA, Ismail-Beigi F, Ambrosius WT; Action to Control Cardiovascular Risk in Diabetes Eye Study Research Group. The effects of medical management on the progression of diabetic retinopathy in persons with type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study. Ophthalmology. 2014 Dec;121(12):2443-51. doi: 10.1016/j.ophtha.2014.07.019. Epub 2014 Aug 29.
Fatemi O, Yuriditsky E, Tsioufis C, Tsachris D, Morgan T, Basile J, Bigger T, Cushman W, Goff D, Soliman EZ, Thomas A, Papademetriou V. Impact of intensive glycemic control on the incidence of atrial fibrillation and associated cardiovascular outcomes in patients with type 2 diabetes mellitus (from the Action to Control Cardiovascular Risk in Diabetes Study). Am J Cardiol. 2014 Oct 15;114(8):1217-22. doi: 10.1016/j.amjcard.2014.07.045. Epub 2014 Jul 30.
Margolis KL, Palermo L, Vittinghoff E, Evans GW, Atkinson HH, Hamilton BP, Josse RG, O'Connor PJ, Simmons DL, Tiktin M, Schwartz AV. Intensive blood pressure control, falls, and fractures in patients with type 2 diabetes: the ACCORD trial. J Gen Intern Med. 2014 Dec;29(12):1599-606. doi: 10.1007/s11606-014-2961-3. Epub 2014 Aug 16.
Gerstein HC, Miller ME, Ismail-Beigi F, Largay J, McDonald C, Lochnan HA, Booth GL; ACCORD Study Group. Effects of intensive glycaemic control on ischaemic heart disease: analysis of data from the randomised, controlled ACCORD trial. Lancet. 2014 Nov 29;384(9958):1936-41. doi: 10.1016/S0140-6736(14)60611-5. Epub 2014 Jul 31.
Margolis KL, O'Connor PJ, Morgan TM, Buse JB, Cohen RM, Cushman WC, Cutler JA, Evans GW, Gerstein HC, Grimm RH Jr, Lipkin EW, Narayan KM, Riddle MC Jr, Sood A, Goff DC Jr. Outcomes of combined cardiovascular risk factor management strategies in type 2 diabetes: the ACCORD randomized trial. Diabetes Care. 2014 Jun;37(6):1721-8. doi: 10.2337/dc13-2334. Epub 2014 Mar 4.
Williamson JD, Launer LJ, Bryan RN, Coker LH, Lazar RM, Gerstein HC, Murray AM, Sullivan MD, Horowitz KR, Ding J, Marcovina S, Lovato L, Lovato J, Margolis KL, Davatzikos C, Barzilay J, Ginsberg HN, Linz PE, Miller ME; Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes Investigators. Cognitive function and brain structure in persons with type 2 diabetes mellitus after intensive lowering of blood pressure and lipid levels: a randomized clinical trial. JAMA Intern Med. 2014 Mar;174(3):324-33. doi: 10.1001/jamainternmed.2013.13656.
Linz PE, Lovato LC, Byington RP, O'Connor PJ, Leiter LA, Weiss D, Force RW, Crouse JR, Ismail-Beigi F, Simmons DL, Papademetriou V, Ginsberg HN, Elam MB. Paradoxical reduction in HDL-C with fenofibrate and thiazolidinedione therapy in type 2 diabetes: the ACCORD Lipid Trial. Diabetes Care. 2014;37(3):686-93. doi: 10.2337/dc13-0790. Epub 2013 Dec 2.
Miller ME, Williamson JD, Gerstein HC, Byington RP, Cushman WC, Ginsberg HN, Ambrosius WT, Lovato L, Applegate WB; ACCORD Investigators. Effects of randomization to intensive glucose control on adverse events, cardiovascular disease, and mortality in older versus younger adults in the ACCORD Trial. Diabetes Care. 2014;37(3):634-43. doi: 10.2337/dc13-1545. Epub 2013 Oct 29.
Fonseca V, McDuffie R, Calles J, Cohen RM, Feeney P, Feinglos M, Gerstein HC, Ismail-Beigi F, Morgan TM, Pop-Busui R, Riddle MC; ACCORD Study Group. Determinants of weight gain in the action to control cardiovascular risk in diabetes trial. Diabetes Care. 2013 Aug;36(8):2162-8. doi: 10.2337/dc12-1391. Epub 2013 Feb 14.
Gerstein HC, Ambrosius WT, Danis R, Ismail-Beigi F, Cushman W, Calles J, Banerji M, Schubart U, Chew EY; ACCORD Study Group. Diabetic retinopathy, its progression, and incident cardiovascular events in the ACCORD trial. Diabetes Care. 2013 May;36(5):1266-71. doi: 10.2337/dc12-1311. Epub 2012 Dec 13.
Reyes-Soffer G, Ngai CI, Lovato L, Karmally W, Ramakrishnan R, Holleran S, Ginsberg HN. Effect of combination therapy with fenofibrate and simvastatin on postprandial lipemia in the ACCORD lipid trial. Diabetes Care. 2013 Feb;36(2):422-8. doi: 10.2337/dc11-2556. Epub 2012 Oct 1.
Barzilay JI, Howard AG, Evans GW, Fleg JL, Cohen RM, Booth GL, Kimel AR, Pedley CF, Cushman WC. Intensive blood pressure treatment does not improve cardiovascular outcomes in centrally obese hypertensive individuals with diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood Pressure Trial. Diabetes Care. 2012 Jul;35(7):1401-5. doi: 10.2337/dc11-1827.
Bonds DE, Miller ME, Dudl J, Feinglos M, Ismail-Beigi F, Malozowski S, Seaquist E, Simmons DL, Sood A. Severe hypoglycemia symptoms, antecedent behaviors, immediate consequences and association with glycemia medication usage: Secondary analysis of the ACCORD clinical trial data. BMC Endocr Disord. 2012 May 30;12:5. doi: 10.1186/1472-6823-12-5.
Sullivan MD, O'Connor P, Feeney P, Hire D, Simmons DL, Raisch DW, Fine LJ, Narayan KM, Ali MK, Katon WJ. Depression predicts all-cause mortality: epidemiological evaluation from the ACCORD HRQL substudy. Diabetes Care. 2012 Aug;35(8):1708-15. doi: 10.2337/dc11-1791. Epub 2012 May 22.
Raisch DW, Feeney P, Goff DC Jr, Narayan KM, O'Connor PJ, Zhang P, Hire DG, Sullivan MD. Baseline comparison of three health utility measures and the feeling thermometer among participants in the Action to Control Cardiovascular Risk in Diabetes trial. Cardiovasc Diabetol. 2012 Jul 11;11:35. doi: 10.1186/1475-2840-11-35.
Bonds DE, Craven TE, Buse J, Crouse JR, Cuddihy R, Elam M, Ginsberg HN, Kirchner K, Marcovina S, Mychaleckyj JC, O'Connor PJ, Sperl-Hillen JA. Fenofibrate-associated changes in renal function and relationship to clinical outcomes among individuals with type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) experience. Diabetologia. 2012 Jun;55(6):1641-50. doi: 10.1007/s00125-012-2524-2. Epub 2012 Mar 27.
Mychaleckyj JC, Craven T, Nayak U, Buse J, Crouse JR, Elam M, Kirchner K, Lorber D, Marcovina S, Sivitz W, Sperl-Hillen J, Bonds DE, Ginsberg HN. Reversibility of fenofibrate therapy-induced renal function impairment in ACCORD type 2 diabetic participants. Diabetes Care. 2012 May;35(5):1008-14. doi: 10.2337/dc11-1811. Epub 2012 Mar 19.
Punthakee Z, Miller ME, Launer LJ, Williamson JD, Lazar RM, Cukierman-Yaffee T, Seaquist ER, Ismail-Beigi F, Sullivan MD, Lovato LC, Bergenstal RM, Gerstein HC; ACCORD Group of Investigators; ACCORD-MIND Investigators. Poor cognitive function and risk of severe hypoglycemia in type 2 diabetes: post hoc epidemiologic analysis of the ACCORD trial. Diabetes Care. 2012 Apr;35(4):787-93. doi: 10.2337/dc11-1855. Epub 2012 Feb 28.
Seaquist ER, Miller ME, Bonds DE, Feinglos M, Goff DC Jr, Peterson K, Senior P; ACCORD Investigators. The impact of frequent and unrecognized hypoglycemia on mortality in the ACCORD study. Diabetes Care. 2012 Feb;35(2):409-14. doi: 10.2337/dc11-0996. Epub 2011 Dec 16.
Genuth S, Ismail-Beigi F. Clinical implications of the ACCORD trial. J Clin Endocrinol Metab. 2012 Jan;97(1):41-8. doi: 10.1210/jc.2011-1679. Epub 2011 Nov 2. Review.
Samaropoulos XF, Light L, Ambrosius WT, Marcovina SM, Probstfield J, Goff DC Jr. The effect of intensive risk factor management in type 2 diabetes on inflammatory biomarkers. Diabetes Res Clin Pract. 2012 Mar;95(3):389-98. doi: 10.1016/j.diabres.2011.09.027. Epub 2011 Oct 22.
Mychaleckyj JC, Farber EA, Chmielewski J, Artale J, Light LS, Bowden DW, Hou X, Marcovina SM. Buffy coat specimens remain viable as a DNA source for highly multiplexed genome-wide genetic tests after long term storage. J Transl Med. 2011 Jun 10;9:91. doi: 10.1186/1479-5876-9-91.
ACCORD Study Group, Gerstein HC, Miller ME, Genuth S, Ismail-Beigi F, Buse JB, Goff DC Jr, Probstfield JL, Cushman WC, Ginsberg HN, Bigger JT, Grimm RH Jr, Byington RP, Rosenberg YD, Friedewald WT. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011 Mar 3;364(9):818-28. doi: 10.1056/NEJMoa1006524.
Ismail-Beigi F, Craven T, Banerji MA, Basile J, Calles J, Cohen RM, Cuddihy R, Cushman WC, Genuth S, Grimm RH Jr, Hamilton BP, Hoogwerf B, Karl D, Katz L, Krikorian A, O'Connor P, Pop-Busui R, Schubart U, Simmons D, Taylor H, Thomas A, Weiss D, Hramiak I; ACCORD trial group. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet. 2010 Aug 7;376(9739):419-30. doi: 10.1016/S0140-6736(10)60576-4. Epub 2010 Jun 30. Erratum in: Lancet. 2010 Oct 30;376(9751):1466.
ACCORD Study Group; ACCORD Eye Study Group, Chew EY, Ambrosius WT, Davis MD, Danis RP, Gangaputra S, Greven CM, Hubbard L, Esser BA, Lovato JF, Perdue LH, Goff DC Jr, Cushman WC, Ginsberg HN, Elam MB, Genuth S, Gerstein HC, Schubart U, Fine LJ. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med. 2010 Jul 15;363(3):233-44. doi: 10.1056/NEJMoa1001288. Epub 2010 Jun 29. Erratum in: N Engl J Med. 2011 Jan 13;364(2):190. N Engl J Med. 2012 Dec 20;367(25):2458.
Strylewicz G, Doctor J. Evaluation of an automated method to assist with error detection in the ACCORD central laboratory. Clin Trials. 2010 Aug;7(4):380-9. doi: 10.1177/1740774510372779. Epub 2010 Jun 22.
Riddle MC, Ambrosius WT, Brillon DJ, Buse JB, Byington RP, Cohen RM, Goff DC Jr, Malozowski S, Margolis KL, Probstfield JL, Schnall A, Seaquist ER; Action to Control Cardiovascular Risk in Diabetes Investigators. Epidemiologic relationships between A1C and all-cause mortality during a median 3.4-year follow-up of glycemic treatment in the ACCORD trial. Diabetes Care. 2010 May;33(5):983-90. doi: 10.2337/dc09-1278.
ACCORD Study Group, Ginsberg HN, Elam MB, Lovato LC, Crouse JR 3rd, Leiter LA, Linz P, Friedewald WT, Buse JB, Gerstein HC, Probstfield J, Grimm RH, Ismail-Beigi F, Bigger JT, Goff DC Jr, Cushman WC, Simons-Morton DG, Byington RP. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010 Apr 29;362(17):1563-74. doi: 10.1056/NEJMoa1001282. Epub 2010 Mar 14. Erratum in: N Engl J Med. 2010 May 6;362(18):1748.
ACCORD Study Group, Cushman WC, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr, Cutler JA, Simons-Morton DG, Basile JN, Corson MA, Probstfield JL, Katz L, Peterson KA, Friedewald WT, Buse JB, Bigger JT, Gerstein HC, Ismail-Beigi F. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010 Apr 29;362(17):1575-85. doi: 10.1056/NEJMoa1001286. Epub 2010 Mar 14.
Pop-Busui R, Evans GW, Gerstein HC, Fonseca V, Fleg JL, Hoogwerf BJ, Genuth S, Grimm RH, Corson MA, Prineas R; Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of cardiac autonomic dysfunction on mortality risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Diabetes Care. 2010 Jul;33(7):1578-84. doi: 10.2337/dc10-0125. Epub 2010 Mar 9.
Miller ME, Bonds DE, Gerstein HC, Seaquist ER, Bergenstal RM, Calles-Escandon J, Childress RD, Craven TE, Cuddihy RM, Dailey G, Feinglos MN, Ismail-Beigi F, Largay JF, O'Connor PJ, Paul T, Savage PJ, Schubart UK, Sood A, Genuth S; ACCORD Investigators. The effects of baseline characteristics, glycaemia treatment approach, and glycated haemoglobin concentration on the risk of severe hypoglycaemia: post hoc epidemiological analysis of the ACCORD study. BMJ. 2010 Jan 8;340:b5444. doi: 10.1136/bmj.b5444.
Bonds DE, Miller ME, Bergenstal RM, Buse JB, Byington RP, Cutler JA, Dudl RJ, Ismail-Beigi F, Kimel AR, Hoogwerf B, Horowitz KR, Savage PJ, Seaquist ER, Simmons DL, Sivitz WI, Speril-Hillen JM, Sweeney ME. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ. 2010 Jan 8;340:b4909. doi: 10.1136/bmj.b4909.
Meier M, Hummel M. Cardiovascular disease and intensive glucose control in type 2 diabetes mellitus: moving practice toward evidence-based strategies. Vasc Health Risk Manag. 2009;5:859-71. Epub 2009 Nov 2. Review.
Murray AM, Hsu FC, Williamson JD, Bryan RN, Gerstein HC, Sullivan MD, Miller ME, Leng I, Lovato LL, Launer LJ; Action to Control Cardiovascular Risk in Diabetes Follow-On Memory in Diabetes (ACCORDION MIND) Investigators. ACCORDION MIND: results of the observational extension of the ACCORD MIND randomised trial. Diabetologia. 2017 Jan;60(1):69-80. Epub 2016 Oct 20.
Zhang Z, Lovato J, Battapady H, Davatzikos C, Gerstein HC, Ismail-Beigi F, Launer LJ, Murray A, Punthakee Z, Tirado AA, Williamson J, Bryan RN, Miller ME. Effect of hypoglycemia on brain structure in people with type 2 diabetes: epidemiological analysis of the ACCORD-MIND MRI trial. Diabetes Care. 2014 Dec;37(12):3279-85. doi: 10.2337/dc14-0973. Epub 2014 Sep 29.
Bryan RN, Bilello M, Davatzikos C, Lazar RM, Murray A, Horowitz K, Lovato J, Miller ME, Williamson J, Launer LJ. Effect of diabetes on brain structure: the action to control cardiovascular risk in diabetes MR imaging baseline data. Radiology. 2014 Jul;272(1):210-6. doi: 10.1148/radiol.14131494. Epub 2014 Apr 29.
Barzilay JI, Lovato JF, Murray AM, Williamson J, Ismail-Beigi F, Karl D, Papademetriou V, Launer LJ. Albuminuria and cognitive decline in people with diabetes and normal renal function. Clin J Am Soc Nephrol. 2013 Nov;8(11):1907-14. doi: 10.2215/CJN.11321112. Epub 2013 Aug 29.
Launer LJ, Miller ME, Williamson JD, Lazar RM, Gerstein HC, Murray AM, Sullivan M, Horowitz KR, Ding J, Marcovina S, Lovato LC, Lovato J, Margolis KL, O'Connor P, Lipkin EW, Hirsch J, Coker L, Maldjian J, Sunshine JL, Truwit C, Davatzikos C, Bryan RN; ACCORD MIND investigators. Effects of intensive glucose lowering on brain structure and function in people with type 2 diabetes (ACCORD MIND): a randomised open-label substudy. Lancet Neurol. 2011 Nov;10(11):969-77. doi: 10.1016/S1474-4422(11)70188-0. Epub 2011 Sep 28.

Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT00000620     History of Changes
Obsolete Identifiers: NCT00182910
Other Study ID Numbers: 123
N01HC95178 ( U.S. NIH Grant/Contract )
N01HC95179 ( U.S. NIH Grant/Contract )
N01HC95180 ( U.S. NIH Grant/Contract )
N01HC95181 ( U.S. NIH Grant/Contract )
N01HC95182 ( U.S. NIH Grant/Contract )
N01HC95183 ( U.S. NIH Grant/Contract )
N01HC95184 ( U.S. NIH Grant/Contract )
IAA#Y1HC9035 ( Other Grant/Funding Number: U.S. Centers for Disease Control )
IAA#Y1HC1010 ( Other Grant/Funding Number: U.S. Centers for Disease Control )
First Submitted: October 27, 1999
First Posted: October 28, 1999
Results First Submitted: September 5, 2014
Results First Posted: September 15, 2014
Last Update Posted: November 22, 2016
Last Verified: November 2014

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):
Diabetes Mellitus, Non-Insulin-Dependent

Additional relevant MeSH terms:
Diabetes Mellitus
Cardiovascular Diseases
Diabetes Mellitus, Type 2
Atherosclerosis
Hypercholesterolemia
Coronary Disease
Coronary Artery Disease
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Myocardial Ischemia
Heart Diseases
Insulin, Globin Zinc
Pioglitazone
Rosiglitazone
Insulin
Insulin Glargine
Insulin Aspart
Insulin Detemir
Hypoglycemic Agents
Simvastatin
Fenofibrate
Benazepril
Candesartan


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