Trial reportJournal of the American College of Cardiology2013

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 and 3 more

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Journal of the American College of Cardiology, 2013. The graph read 1 number from its abstract, feeding 1 cell of the map, but it casts no vote: it is a later paper about NCT00120289, whose primary report (PMID 22085343) speaks for the trial. It reports registered trial NCT00120289. Cited by 54 papers, 2 of them syntheses that pooled it.

1number the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 2 pooled it
24.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

Read, but not usablea number the graph found but could not read as for or against

Lipidscomparator not stated · ascvd, dyslipidemiafeeds one cell of the map
HR 0.74p = 0.073
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).

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

Other lipid agents×lipids

No readable resultOpen on the map →What to test next →

28 readable studies in this cell: 17 favour the treatment, 2 find no difference, 9 favour the comparator.

Belief with this paper
0.50contested · 15 families support, 6 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT004793881,216 enrolled · 2007
Δ -4.50-7.70 to -1.30
NCT00862251808 enrolled · 2009
Percent change in least-square means -14.8-19.6 to -9.91
NCT00485758796 enrolled · 2007
Δ -17.9-21.4 to -14.4
NCT00730132712 enrolled · 2008
Δ -5.75-9.43 to -2.07
NCT01763827615 enrolled · 2013
Δ -39.3-43.3 to -35.3
NCT01984424511 enrolled · 2013
Δ -37.8-42.3 to -33.3
NCT06005597407 enrolled · 2024
Least Squares (LS) Means -27.9-37.5 to -18.4
NCT03337308382 enrolled · 2017
Δ -38.0-46.5 to -29.6
NCT02227784366 enrolled · 2014
Δ -6.14-12.2 to -0.22
NCT01763905307 enrolled · 2013
Δ -38.1-43.7 to -33.0
NCT03001076269 enrolled · 2016
Δ -28.4-34.4 to -22.5

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00120289 phase3terminated

AIM HIGH: Niacin Plus Statin to Prevent Vascular Events

Ran2005Enrolled3,414Registered outcomes4Posted comparisons4ConditionsAtherosclerosis, Cardiovascular Diseases, Cerebrovascular Accident, Coronary DiseaseArmsExtended release niacin, simvastatin
Open the trial in the graph
5 · Its place in the literature

Who cites it

54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 182 citations in OpenAlex.

  1. Niacin for primary and secondary prevention of cardiovascular events.The Cochrane database of systematic reviews · 2017 · on this map
    Pooled it
  2. Statins for primary prevention of venous thromboembolism.The Cochrane database of systematic reviews · 2014
    Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. Trial
  7. Trial
  8. Trial
  9. Trial
  10. Trial
  11. Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Lipoprotein(a) as a Risk Factor for Cardiovascular Diseases: Pathophysiology and Treatment Perspectives.International journal of environmental research and public health · 2023
    Review
  19. Omega-3 Fatty Acids in Arterial Hypertension: Is There Any Good News?International journal of molecular sciences · 2023
    Review
  20. Article
6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

13 authors at 9 institutions in 2 countries.

John R GuytonDepartment of Medicine, Duke University Medical Center, Durham, North Carolina. Electronic address: john.guyton@duke.edu.
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
University of Washington · USAptevo Therapeutics (United states) · USAlbany Stratton VA Medical Center Albany · USDuke University · USNational Heart Lung and Blood Institute · USSyracuse University · USUniversity of Calgary · CAUniversity of California, Irvine · USUniversity of Miami · US

Funding

AIM-HIGHU01HL081649 · NHLBI · AXIO RESEARCH, LLC · PI MCBRIDE, RUTH M · 2005 to 2010
$15.1M
AIM HIGH: Niacin Plus Statin to Prevent Vascular EventsU01HL081616 · NHLBI · UNIVERSITY OF WASHINGTON · PI PROBSTFIELD, JEFFREY LYNN · 2005 to 2010
$6.0M
NHLBI NIH HHS U01 HL081616NHLBI NIH HHS U01 HL081649
8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

objectivesThis 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.

backgroundDuring 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.

methodsSubjects 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.

resultsCV 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.

conclusionsBaseline 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).

Indexed as

Global HealthAgedAnticholesteremic AgentsBiomarkersCardiovascular DiseasesCholesterol, HDLDouble-Blind MethodDrug Therapy, CombinationFemaleFollow-Up StudiesHumansLipoproteinsMaleMetabolic SyndromeMiddle AgedNiacinAnticholesteremic AgentsBiomarkersCholesterol, HDLLipoproteinsNiacinTriglyceridescardiovascularcardiovascular eventsclinical trialCVERextended-releaseGPR109AG-protein–coupled receptor 109Ahazard ratioHDL-Chigh-density lipoprotein cholesterolHRLDL-Clipoproteinslow-density lipoprotein cholesterolniacinTGtriglyceride

Identifiers

PMID23916935
PMCPMC3862446
OpenAlexW2189339462

What Socratic holds

Texttitle and abstract
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.