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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Clinical Trials Review Committee (CLTR)
Program Officer
Desvigne-Nickens, Patrice
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Axio Research, LLC
United States
Zip Code
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

Showing the most recent 10 out of 12 publications