AIM-HIGH is a multicenter controlled clinical trial designed to test whether the drug combination extended release niacin plus simvastatin is superior to simvastatin alone, at comparable levels of in-treatment LDLcholesterol (LDL-C), for delaying the time to a first major cardiovascular (CV) disease outcome over a 4-year median follow-up in patients with atherogenic dyslipidemia. Prior 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). The proposed study is needed to confirm whether statin-niacin combination therapy, designed to target a wider spectrum of dyslipidemic factors in addition to LDL-C, will provide a more substantial (>50%) reduction of CV events. Epidemiologic studies confirm the high prevalance of atherogenic dyslipidemia and its impact on CV event rates. Preliminary clinical trials suggest that targeting these factors with dylipidemic therapy will reduce CV events. The proposed study will enroll men and women >45 years old at high risk of recurrent CV events by virtue of having established CV disease together with the two dyslipidemic elements of metabolic syndrome - low HDL-cholesterol (HDL-C) [<=40 mg/dl] and high triglycerides (TG) [>=150 mg/dl]. 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-hemorrhagic stroke. The 3300-patient sample, to be recruited in 54 centers in US and Canada, will have >90% power for the primary endpoint, and up to 85% power to confirm a 29% risk reduction, relative to statin monotherapy, for the triple endpoint above. In summary, statins have little effect on HDL-C orTG, and only moderately reduce CV risk.
AIM -HIGH is designed to confirm a substantially greater benefit from """"""""complete"""""""" lipid therapy using statins plus niacin.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project--Cooperative Agreements (U01)
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Clinical Trials Review Committee (CLTR)
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Desvigne-Nickens, Patrice
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University of Washington
Internal Medicine/Medicine
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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
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
AIM-HIGH Investigators (2011) 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 partici Am Heart J 161:538-43

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