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)

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

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Objectives 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. Background 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. Methods 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. Results 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. Conclusions 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).

Original languageEnglish
Pages (from-to)1580-1584
Number of pages5
JournalJournal of the American College of Cardiology
Volume62
Issue number17
DOIs
StatePublished - Oct 22 2013

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Niacin
Lipoproteins
Triglycerides
LDL Cholesterol
HDL Cholesterol
Global Health
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Simvastatin
Therapeutics
Acute Coronary Syndrome
Proportional Hazards Models
Blood Vessels
Cardiovascular Diseases
Stroke
Myocardial Infarction
Cholesterol
Placebos

Keywords

  • cardiovascular events
  • clinical trial
  • GPR109A
  • lipoproteins
  • niacin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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). / Guyton, John R.; Slee, April E.; Anderson, Todd; Fleg, Jerome L.; Goldberg, Ronald B; Kashyap, Moti L.; Marcovina, Santica M.; Nash, Stephen D.; O'Brien, Kevin D.; Weintraub, William S.; Xu, Ping; Zhao, Xue Qiao; Boden, William E.

In: Journal of the American College of Cardiology, Vol. 62, No. 17, 22.10.2013, p. 1580-1584.

Research output: Contribution to journalArticle

Guyton, John R. ; Slee, April E. ; Anderson, Todd ; Fleg, Jerome L. ; Goldberg, Ronald B ; Kashyap, Moti L. ; Marcovina, Santica M. ; Nash, Stephen D. ; O'Brien, Kevin D. ; Weintraub, William S. ; Xu, Ping ; Zhao, Xue Qiao ; Boden, William E. / 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). In: Journal of the American College of Cardiology. 2013 ; Vol. 62, No. 17. pp. 1580-1584.
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abstract = "Objectives 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. Background 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. Methods 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. Results 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. Conclusions 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).",
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T2 - The aim-high trial (atherothrombosis intervention in metabolic syndrome with low HDL/high triglycerides and impact on global health outcomes)

AU - Guyton, John R.

AU - Slee, April E.

AU - Anderson, Todd

AU - Fleg, Jerome L.

AU - Goldberg, Ronald B

AU - Kashyap, Moti L.

AU - Marcovina, Santica M.

AU - Nash, Stephen D.

AU - O'Brien, Kevin D.

AU - Weintraub, William S.

AU - Xu, Ping

AU - Zhao, Xue Qiao

AU - Boden, William E.

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N2 - Objectives 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. Background 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. Methods 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. Results 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. Conclusions 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).

AB - Objectives 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. Background 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. Methods 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. Results 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. Conclusions 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).

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