AIM-HIGH is a multicenter controlled clinical trial designed to test the hypothesis that the drug combination of extended-release (ER-) niacin plus simvastatin is superior to simvastatin alone, at comparable levels of intreatment LDL-cholesterol, for delaying the time to first occurrence of clinically relevant cardiovascular (CV) disease outcomes over a 4-year median follow-up. Large 5-yr clinical trials have found only 25-35% CV risk reduction using statin monotherapy (i.e., event rate 2/3 to 3/4 of placebo rate). Thus, this study is needed to confirm the more substantial (>50%) treatment benefit predicted for the statin-niacin combination by epidemiology and by preliminary clinical trials. The target population is men and women >45 years old with established CV disease and at higher risk due to the two dyslipidemic elements of metabolic syndrome (MS) -- low HDL-cholesterol (HDL-C) [40 mg/dl or less] and high triglycerides (TG) [150 mg/dl or greater]. The proposed study specifically aims to test this hypothesis for the primary composite clinical endpoint of CV death, nonfatal myocardial infarction (Ml), non-hemorrhagic stroke, or hospitalization for high-risk acute coronary syndrome with objective evidence of ischemia (troponin-positive or ST-segment deviation). A secondary endpoint is the composite of CV death, non-fatal Ml, or non-hemorr-hagic stroke. The above hypotheses will also be tested among the very large subgroup of these patients who meet the current or future evolving criteria for metabolic syndrome. The 3300-patient sample, to be recruited in 54 centers in US and Canada, will have up to 85% power to confirm a 29% risk reduction, relative to statin monotherapy, for the rigorous triple endpoint above, and >90% power for the primary endpoint. This companion grant describes the Clinical Trial Center for AIM-HIGH and methodologies for trial coordination, site identification, initiation, and management, data management and biostatistical support.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL081649-06
Application #
7849040
Study Section
Clinical Trials Review Committee (CLTR)
Program Officer
Desvigne-Nickens, Patrice
Project Start
2005-09-01
Project End
2013-04-30
Budget Start
2010-05-01
Budget End
2013-04-30
Support Year
6
Fiscal Year
2010
Total Cost
$5,078,168
Indirect Cost
Name
Axio Research, LLC
Department
Type
DUNS #
172217635
City
Seattle
State
WA
Country
United States
Zip Code
98121
Tuteja, Sony; Wang, Lu; Dunbar, Richard L et al. (2017) Genetic coding variants in the niacin receptor, hydroxyl-carboxylic acid receptor 2, and response to niacin therapy. Pharmacogenet Genomics 27:285-293
Lyubarova, Radmila; Robinson, Jennifer G; Miller, Michael et al. (2017) Metabolic syndrome cluster does not provide incremental prognostic information in patients with stable cardiovascular disease: A post hoc analysis of the AIM-HIGH trial. J Clin Lipidol 11:1201-1211
Goldberg, Ronald B; Bittner, Vera A; Dunbar, Richard L et al. (2016) Effects of Extended-Release Niacin Added to Simvastatin/Ezetimibe on Glucose and Insulin Values in AIM-HIGH. Am J Med 129:753.e13-22
O'Brien, Kevin D; Hippe, Daniel S; Chen, Huijun et al. (2016) Longer duration of statin therapy is associated with decreased carotid plaque vascularity by magnetic resonance imaging. Atherosclerosis 245:74-81
Albers, John J; Slee, April; Fleg, Jerome L et al. (2016) Relationship of baseline HDL subclasses, small dense LDL and LDL triglyceride to cardiovascular events in the AIM-HIGH clinical trial. Atherosclerosis 251:454-459
Kalil, Roberto S; Wang, Jeffrey H; de Boer, Ian H et al. (2015) Effect of extended-release niacin on cardiovascular events and kidney function in chronic kidney disease: a post hoc analysis of the AIM-HIGH trial. Kidney Int 87:1250-7
Anderson, Todd J; Boden, William E; Desvigne-Nickens, Patrice et al. (2014) Safety profile of extended-release niacin in the AIM-HIGH trial. N Engl J Med 371:288-90
Guyton, John R; Slee, April E; Anderson, Todd et al. (2013) 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 62:1580-4
Albers, John J; Slee, April; O'Brien, Kevin D et al. (2013) 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 62:1575-9
Teo, Koon K; Goldstein, Larry B; Chaitman, Bernard R et al. (2013) 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 44:2688-93

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