Niacin Plus Statin to Prevent Vascular Events

Study Description

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Brief Summary:

The purpose of this study is to determine whether raising "good cholesterol" with a drug based on the vitamin niacin, while lowering "bad cholesterol" with a statin drug, can prevent more heart disease than the statin alone.

Condition or disease	Intervention/treatment	Phase
Cardiovascular Diseases; Heart Diseases; Cerebrovascular Accident; Coronary Disease; Atherosclerosis; Myocardial Infarction	Drug: Extended release niacin; Drug: Simvastatin	Phase 3

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Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	3414 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Prevention
Official Title:	AIM HIGH: Niacin Plus Statin to Prevent Vascular Events
Study Start Date :	September 2005
Actual Primary Completion Date :	September 2012
Actual Study Completion Date :	December 2012

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Combination Therapy; Extended release niacin plus simvastatin	Drug: Extended release niacin; 2,000 mg/day or 1,500 mg/day if higher dose not tolerated; Other Name: Niaspan Drug: Simvastatin; Dose adjusted to achieve LDL-C 40 mg/dL - 80 mg/dL, adding ezetimibe (10 mg/day) if needed to achieve LDL-C target; Other Name: Zocor
Active Comparator: Monotherapy; Simvastatin alone	Drug: Simvastatin; Dose adjusted to achieve LDL-C 40 mg/dL - 80 mg/dL, adding ezetimibe (10 mg/day) if needed to achieve LDL-C target; Other Name: Zocor

Outcome Measures

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Primary Outcome Measures :

1. Composite End Point of CHD Death, Nonfatal MI, Ischemic Stroke, Hospitalization for Non-ST Segment Elevation Acute Coronary Syndrome (ACS), or Symptom-driven Coronary or Cerebral Revascularization [ Time Frame: Time to first event measured from date of randomization through last follow-up visit (common termination) for an average of 36 months follow-up, maximum 66 months. ]

Secondary Outcome Measures :

1. Composite Endpoint of CHD Death, Non-fatal MI, High-risk ACS or Ischemic Stroke [ Time Frame: Time to first event measured from date of randomization through last follow-up visit (common termination) for an average of 36 months follow-up, maximum 66 months ]
2. Composite Endpoint of CHD Death, Non-fatal MI, or Ischemic Stroke [ Time Frame: Time to first event measured from date of randomization through last follow-up visit (common termination) for an average of 36 months follow-up, maximum 66 months ]
3. Cardiovascular Mortality [ Time Frame: Time to first event measured from date of randomization through last follow-up visit (common termination), for an average of 36 months follow-up, maximum 66 months. ]

Eligibility Criteria

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Ages Eligible for Study:	45 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Men and women aged 45 and older with established vascular disease and atherogenic dyslipidemia
• Established vascular disease defined as one or more of the following: (1) documented coronary artery disease (CAD); (2) documented cerebrovascular or carotid disease; (3) documented symptomatic peripheral arterial disease (PAD)
• Atherogenic dyslipidemia defined as: (1) LDL-C of less than or equal to 160 mg/dL (4.1 mmol/L); (2) HDL-C of less than or equal to 40 mg/dL (1.0 mmol/L) for men or less than or equal to 50 mg/dL (1.3 mmol/L) for women; (3) TG greater than or equal to 150 mg/dL (1.7 mmol/L) and less than or equal to 400 mg/dL (4.5 mmol/L)
• For patients entering the trial on a statin: (1) the upper limit for LDL-C is adjusted according to the specific statin and statin dose; (2) HDL-C of less than or equal to 42 mg/dL (1.1 mmol/L) for men or less than or equal to 53 mg/dL (1.4 mmol/L) for women; (3) TG greater than or equal to 125 mg/dL (1.4 mmol/L) and less than or equal to 400 mg/DL (4.5 mmol/L)

Exclusion Criteria:

• Coronary artery bypass graft (CABG) surgery within 1 year of planned enrollment (run-in phase)
• Percutaneous coronary intervention (PCI) within 4 weeks of planned enrollment (run-in phase)
• Hospitalization for acute coronary syndrome and discharge within 4 weeks of planned enrollment (run-in phase)
• Fasting glucose greater than 180 mg/dL (10 mmol/L) or hemoglobin A1C greater than 9%
• For patients with diabetes, inability or refusal to use a glucometer for home monitoring of blood glucose
• Concomitant use of drugs with a high probability of increasing the risk for hepatotoxicity or myopathy, such as those predominantly metabolized by cytochrome P450 system 3A4, including but not limited to cyclosporine, gemfibrozil, fenofibrate, itraconazole, ketoconazole, HIV protease inhibitors, nefazodone, verapamil, amiodarone; lipid-lowering drugs (other than the investigational drugs) such as statins, bile-acid sequestrants, cholesterol absorption inhibitors (e.g., ezetimibe), fibrates or high-dose, antioxidant vitamins (vitamins C, E, or beta carotene) that can interfere with the HDL-raising effect of niacin

Contacts and Locations

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Locations

United States, Alabama
Cardiovascular Associates, P.C.
Birmingham, Alabama, United States, 35213
University of Alabama, Birmingham
Birmingham, Alabama, United States, 35294
Clinical Research Consultants, Inc.
Hoover, Alabama, United States, 35216
United States, Arizona
Carl T. Hayden VAMC Phoenix Medical Service
Pheonix, Arizona, United States, 85012
Cardiovascular Consultants Ltd
Phoenix, Arizona, United States, 85015
Diabetes Center of Excellence
Phoenix, Arizona, United States, 85016
Tucson Clinical Research (Eastside Site)
Tucson, Arizona, United States, 85712
Tucson Clinical Research (Northwest Site)
Tucson, Arizona, United States, 85741
United States, Arkansas
University of Arkansas
Little Rock, Arkansas, United States, 72205
United States, California
Providence Saint Joseph Medical Center
Burbank, California, United States, 91505
VA Long Beach Healthcare System
Long Beach, California, United States, 90822
Providence Holy Cross Medical Center
Mission Hills, California, United States, 91345
United States, Delaware
Christiana Care Health Services
Newark, Delaware, United States, 19718
United States, Florida
University of Miami
Miami, Florida, United States, 33136
Heart & Vascular Research Center
Sarasota, Florida, United States, 34239
James A. Haley Veteran's Hospital
Tampa, Florida, United States, 33612
United States, Idaho
Idaho State University
Pocatello, Idaho, United States, 83201
United States, Indiana
Parkview Research Center
Fort Wayne, Indiana, United States, 46805
United States, Iowa
Iowa Heart Center, P.C.
Des Moines, Iowa, United States, 50314
Lipid Research Clinic, University of Iowa
Iowa City, Iowa, United States, 52240
United States, Maine
Maine Center for Lipids & Cardiovascular Health
Scarborough, Maine, United States, 04074
United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21201
Johns Hopkins University
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Pentucket Medical Associates
Haverhill, Massachusetts, United States, 01830
United States, Michigan
Veterans Affairs Health System of Ann Arbor, Michigan
Ann Arbor, Michigan, United States, 48105
Grunberger Diabetes Institute
Bloomfield Hills, Michigan, United States, 48302
United States, Minnesota
Berman Center for Outcomes and Clinical Research
Minneapolis, Minnesota, United States, 55404
HealthPartners Riverside Clinic
Minneapolis, Minnesota, United States, 55454
Mayo Clinic
Rochester, Minnesota, United States, 55905
Phalen Village Clinic
St. Paul, Minnesota, United States, 55106
University of Minnesota
Twin Cities, Minnesota, United States, 55414
United States, Mississippi
G.V. (Sonny) Montgomery VAMC
Jackson, Mississippi, United States, 39216
United States, Missouri
St. Louis University
St. Louis, Missouri, United States, 63104
United States, Nebraska
Alegent Health Heart & Vascular Specialists
Papillion, Nebraska, United States, 68046
United States, New Jersey
Cooper Clinical Trials Center
Cherry Hill, New Jersey, United States, 08034
Cardiovascular Associates of the Delaware Valley
Elmer, New Jersey, United States, 08318
UMDNJ -Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903
United States, New Mexico
New Mexico VA Healthcare Systems
Albuquerque, New Mexico, United States, 87108
United States, New York
Kaleida Health/Diabetes Center
Buffalo, New York, United States, 14209
Mid Valley Cardiology
Kingston, New York, United States, 12401
VA New York Harbor Healthcare System
New York, New York, United States, 10010
Columbia University
New York, New York, United States, 10032
Syracuse Preventive Cardiology
Syracuse, New York, United States, 13202
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Wake Forest University - Geriatrics/Gerontology
Greensboro, North Carolina, United States, 27157
Wake Forest University Health Sciences - Department of Cardiology
Winston-Salem, North Carolina, United States, 27157
Wake Forest University School of Medicine - Internal Medicine/Endocrinology
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Sterling Research Group, Ltd.
Cincinnati, Ohio, United States, 45219
St Vincent Charity Hospital - The Center for Vascular Health
Cleveland, Ohio, United States, 44115
North Ohio Research, Ltd.
Sandusky, Ohio, United States, 44870
United States, Oregon
Portland VA Medical Center
Portland, Oregon, United States, 97239
United States, Pennsylvania
Philadelphia VA Medical Center
Philadelphia, Pennsylvania, United States, 19104
Pennsylvania Cardiology Associates
Philadelphia, Pennsylvania, United States, 19106
Cardiology Consultants of Philadelphia
Philadelphia, Pennsylvania, United States, 19148
United States, Rhode Island
Women's Cardiac Center at The Miriam Hospital
Providence, Rhode Island, United States, 02906
United States, South Carolina
Internal Medicine Associates of Greenville
Greenville, South Carolina, United States, 29607
United States, Tennessee
VAMC Memphis - Hypertension/Lipid Research Clinic
Memphis, Tennessee, United States, 38104
United States, Texas
Kelsey Research Foundation
Houston, Texas, United States, 77005
Baylor College of Medicine
Houston, Texas, United States, 77030
Methodist Hospital
Houston, Texas, United States, 77030
United States, Utah
Intermountain Medical Center
Murray, Utah, United States, 84157
United States, Virginia
University of Virginia - UVA Cardiology
Charlottesville, Virginia, United States, 22908
McGuire VA Medical Center
Richmond, Virginia, United States, 23249
United States, Washington
University of Washington, Northwest Lipid Research Center
Seattle, Washington, United States, 98104
University of Washington, Coronary Atherosclerosis Research Lab
Seattle, Washington, United States, 98105
VA Cardiology Research
Seattle, Washington, United States, 98108
Washington State University
Spokane, Washington, United States, 99202
United States, Wisconsin
CARE Foundation, Inc.
Wausau, Wisconsin, United States, 54401
Canada, Alberta
Heart Health Institute
Calgary, Alberta, Canada, T2E 7C5
Foothills Medical Centre
Calgary, Alberta, Canada, T2N 2T9
Royal Alexandra Hospital
Edmonton, Alberta, Canada, T5H 3V9
Canada, British Columbia
Vancouver Hospital
Vancouver, British Columbia, Canada, V5Z 1M9
Victoria Heart Institute
Victoria, British Columbia, Canada, V8R 4R2
Canada, Manitoba
Health Sciences Center, Diabetes Research Group
Winnipeg, Manitoba, Canada, R3E 3R4
Canada, New Brunswick
New Brunswick Heart Center
St John, New Brunswick, Canada, E2L 4L2
Canada, Newfoundland and Labrador
Memorial University of Newfoundland
St. John's, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Center
Halifax, Nova Scotia, Canada, B3H 3A6
Cardiology Associates VRH
Kentville, Nova Scotia, Canada, B4N 5E3
Canada, Ontario
Cambridge Cardiac Care Center
Cambridge, Ontario, Canada, N1R 6V6
McConnell Medical Center
Cornwall, Ontario, Canada, K6H 4M4
Hamilton Health Sciences - General Site
Hamilton, Ontario, Canada, L8L 2X2
LHSC University Hospital
London, Ontario, Canada, N6A 5A5
Newmarket Cardiology Research Group
Newmarket, Ontario, Canada, L3Y 8C3
Sudbury Cardiovascular Research
Sudbury, Ontario, Canada, P3E 2N8
St. Michael's Hospital Health Centre
Toronto, Ontario, Canada, M5C 2T2
Canada, Quebec
Clinique de Cardiologie de Lévis
Lévis, Quebec, Canada, G6V 4Z5
Montreal Heart Institute
Montreal, Quebec, Canada, H1T 1C8
Clinique des maladies lipidiques de Québec
Québec, Quebec, Canada, G1V 4M6
CSSS Beauce
St-Georges de Beauce, Quebec, Canada, G5Y 4T8
CSSS du Sud de Lanaudière - Hôpital Pierre-Le Gardeur
Terrebonne, Quebec, Canada, J6V 2H2
Canada
Recherches Clinicar
Quebec, Canada, G1J 1Z6

Sponsors and Collaborators

Axio Research. LLC

National Heart, Lung, and Blood Institute (NHLBI)

Abbott

Investigators

Study Director:	Ruth McBride	Axio Research Corporation
Principal Investigator:	William E. Boden, MD	Samuel S. Stratton VA Medical Center
Principal Investigator:	Jeffrey Probstfield, MD	University of Washington

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

AIM-HIGH Web site for patients 

Study Data/Documents: Individual Participant Data Set 

Identifier: AIM-HIGH
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.

Study Protocol 

Identifier: AIM-HIGH

Study forms 

Identifier: AIM-HIGH

Publications of Results:

AIM-HIGH Investigators, Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, McBride R, Teo K, Weintraub W. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011 Dec 15;365(24):2255-67. doi: 10.1056/NEJMoa1107579. Epub 2011 Nov 15. Erratum in: N Engl J Med. 2012 Jul 12;367(2):189.

Teo KK, Goldstein LB, Chaitman BR, Grant S, Weintraub WS, Anderson DC, Sila CA, Cruz-Flores S, Padley RJ, Kostuk WJ, Boden WE; AIM-HIGH Investigators. Extended-release niacin therapy and risk of ischemic stroke in patients with cardiovascular disease: the Atherothrombosis Intervention in Metabolic Syndrome with low HDL/High Triglycerides: Impact on Global Health Outcome (AIM-HIGH) trial. Stroke. 2013 Oct;44(10):2688-93. doi: 10.1161/STROKEAHA.113.001529. Epub 2013 Jul 23.

Albers JJ, Slee A, O'Brien KD, Robinson JG, Kashyap ML, Kwiterovich PO Jr, Xu P, Marcovina SM. Relationship of apolipoproteins A-1 and B, and lipoprotein(a) to cardiovascular outcomes: the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes). J Am Coll Cardiol. 2013 Oct 22;62(17):1575-9. doi: 10.1016/j.jacc.2013.06.051. Epub 2013 Aug 21.

Guyton JR, Slee AE, Anderson T, Fleg JL, Goldberg RB, Kashyap ML, Marcovina SM, Nash SD, O'Brien KD, Weintraub WS, Xu P, Zhao XQ, Boden WE. Relationship of lipoproteins to cardiovascular events: the AIM-HIGH Trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes). J Am Coll Cardiol. 2013 Oct 22;62(17):1580-4. doi: 10.1016/j.jacc.2013.07.023. Epub 2013 Jul 31.

Other Publications:

AIM-HIGH Investigators. The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol: baseline characteristics of study participants. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: impact on Global Health outcomes (AIM-HIGH) trial. Am Heart J. 2011 Mar;161(3):538-43. doi: 10.1016/j.ahj.2010.12.007. Epub 2011 Feb 2.

AIM-HIGH Investigators. The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol Rationale and study design. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH). Am Heart J. 2011 Mar;161(3):471-477.e2. doi: 10.1016/j.ahj.2010.11.017. Epub 2011 Feb 2.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

O'Brien KD, Hippe DS, Chen H, Neradilek MB, Probstfield JL, Peck S, Isquith DA, Canton G, Yuan C, Polissar NL, Zhao XQ, Kerwin WS. Longer duration of statin therapy is associated with decreased carotid plaque vascularity by magnetic resonance imaging. Atherosclerosis. 2016 Feb;245:74-81. doi: 10.1016/j.atherosclerosis.2015.11.032. Epub 2015 Dec 1.

Responsible Party:	Ruth McBride, Co-Director, Coordinating Center, Axio Research. LLC
ClinicalTrials.gov Identifier:	NCT00120289 History of Changes
Other Study ID Numbers:	226; U01HL081649 ( U.S. NIH Grant/Contract ); U01HL081616 ( U.S. NIH Grant/Contract )
First Posted:	July 15, 2005
Results First Posted:	June 17, 2015
Last Update Posted:	April 6, 2016
Last Verified:	March 2016

Additional relevant MeSH terms:

Infarction; Cardiovascular Diseases; Heart Diseases; Myocardial Infarction; Atherosclerosis; Coronary Disease; Coronary Artery Disease; Stroke; Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases	Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Simvastatin; Niacin; Niacinamide; Nicotinic Acids; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors