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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).

Journal of the American College of Cardiology (2013-08-07)
John R Guyton, April E Slee, Todd Anderson, Jerome L Fleg, Ronald B Goldberg, Moti L Kashyap, Santica M Marcovina, Stephen D Nash, Kevin D O'Brien, William S Weintraub, Ping Xu, Xue-Qiao Zhao, William E Boden
ABSTRACT

This study sought to examine the relationship between niacin treatment, lipoproteins, and cardiovascular (CV) outcomes in this secondary analysis of the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes) trial. During a 3-year follow-up in 3,414 patients with established CV disease and low high-density lipoprotein cholesterol (HDL-C) levels, combined niacin + low-density lipoprotein cholesterol (LDL-C)-lowering therapy did not reduce CV events compared with LDL-C-lowering therapy alone. Subjects taking simvastatin and/or ezetimibe were randomized to receive extended-release (ER) niacin 1,500 to 2,000 mg or minimal immediate-release niacin (≤ 150 mg) as placebo at bedtime. LDL-C levels in both groups were maintained from 40 to 80 mg/dl. Hazard ratios were estimated by using Cox proportional hazards models for relationships between lipoproteins and the composite endpoint of CV death, myocardial infarction, acute coronary syndrome, ischemic stroke, or symptom-driven revascularization. CV outcomes were not associated with ER niacin in any baseline lipoprotein tertile. In a subset of patients in both the highest triglyceride (≥ 198 mg/dl) and lowest HDL-C (<33 mg/dl) tertiles, ER niacin showed a trend toward benefit (hazard ratio: 0.74, p = 0.073). In-trial LDL-C levels, non-HDL-C levels, and the total cholesterol/HDL-C ratio were positively associated with CV events in the control group, but these relationships were absent in the ER niacin group. Baseline lipoprotein tertiles did not predict differential benefit or harm with ER niacin added to LDL-C-lowering therapy, but a small dyslipidemic subgroup may benefit. ER niacin attenuated expected relationships of lipoprotein risk factors with CV events, raising the possibility that nonlipoprotein actions of niacin could affect risk. (Niacin Plus Statin to Prevent Vascular Events [AIM-HIGH]; NCT00120289).

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Nicotinic acid, ≥98%
Sigma-Aldrich
Nicotinic acid, meets USP testing specifications
Sigma-Aldrich
Nicotinic acid, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥98%
Sigma-Aldrich
Nicotinic acid, ≥99.5% (HPLC)
Supelco
Nicotinic acid, analytical standard
Supelco
Niacin (Nicotinic Acid), Pharmaceutical Secondary Standard; Certified Reference Material