Evidence map›Statins × lipids›PMID 22461416›Full record

Trial reportCirculation2012

Determinants of residual risk in secondary prevention patients treated with high- versus low-dose statin therapy: the Treating to New Targets (TNT) study.

Samia Mora, Nanette K Wenger, David A Demicco, Andrei Breazna, S Matthijs Boekholdt, Benoit J Arsenault, Prakash Deedwania, John J P Kastelein, David D Waters

Registry-linked trialOpen access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Circulation, 2012. The graph read 3 numbers from its abstract, feeding 1 cell of the map, but it casts no vote: the report of the main result of NCT00327691 is not on the map. It also reports 3 associations that do not count as treatment evidence, such as HR 0.91 (0.84 to 0.99) for lipids. It reports registered trial NCT00327691. Cited by 78 papers, 3 of them syntheses that pooled it.

3numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 3 pooled it
17.3field-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

Lipidsan association or prognostic statement, not a treatment comparison · head-to-head · dyslipidemia, hypertensionfeeds one cell of the map
HR 0.910.84 to 0.99
Determinants of decreased risk were high-dose statin (aHR, 0.82; 95% CI, 0.70-0.94), aspirin use (aHR, 0.67; 95% CI, 0.56-0.81), and baseline apolipoprotein A-I (aHR, 0.91; 95% CI, 0.84-0.99 per 25 mg/dL).
FeedsStatins×lipids
Lipidsan association or prognostic statement, not a treatment comparison · head-to-head · dyslipidemia, hypertensionfeeds one cell of the map
HR 0.670.56 to 0.81
Determinants of decreased risk were high-dose statin (aHR, 0.82; 95% CI, 0.70-0.94), aspirin use (aHR, 0.67; 95% CI, 0.56-0.81), and baseline apolipoprotein A-I (aHR, 0.91; 95% CI, 0.84-0.99 per 25 mg/dL).
FeedsStatins×lipids
Lipidsan association or prognostic statement, not a treatment comparison · head-to-head · dyslipidemia, hypertensionfeeds one cell of the map
HR 0.820.70 to 0.94
Determinants of decreased risk were high-dose statin (aHR, 0.82; 95% CI, 0.70-0.94), aspirin use (aHR, 0.67; 95% CI, 0.56-0.81), and baseline apolipoprotein A-I (aHR, 0.91; 95% CI, 0.84-0.99 per 25 mg/dL).
FeedsStatins×lipids

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.

Statins×lipids

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

38 readable studies in this cell: 25 favour the treatment, 5 find no difference, 8 favour the comparator.

Belief with this paper
0.50contested · 21 families support, 7 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT002899002,340 enrolled · 2006
Δ -13.2-16.8 to -9.60
Effect of evolocumab or ezetimibe added to moderate- or high-intensity…PMID 24825642 · 2,067 enrolled · 2013
reduced -66.0-73.0 to -58.0
NCT02546323543 enrolled · 2015
Δ -35.5-40.2 to -30.7
NCT01678820299 enrolled · 2012
Δ 0.50-4.80 to 5.80
NCT01218204287 enrolled · 2010
Δ 5.47-15.7 to 26.7
Lipid-Lowering Effect and Safety of Ezetimibe and Atorvastatin 5 mg in…PMID 40357888 · 252 enrolled · 2022
Δ -47.6
NCT0093525931 enrolled · 2009
Δ -51.7
Effect of Patient Financial Incentives on Statin Adherence and Lipid C…PMID 33034639 · 2020
reductions -33.6-38.8 to -28.4
Icosabutate, a Structurally Engineered Fatty Acid, Improves the Cardio…PMID 27160246 · 2016
Δ -7.40
Evidence for statin pleiotropy in humans: differential effects of stat…PMID 19075102 · 2009
RR 38.0
Efficacy and safety of fluvastatin in patients with non-insulin-depend…PMID 8198023 · 1994
decrease -24.3
Rosuvastatin in older patients with systolic heart failure.PMID 17984166 · 2007
Δ 45.0

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.

NCT00327691 phase4completed

The Effect Of LDL-Cholesterol, Lowering Beyond Currently Recommended Minimum Targets On Coronary Heart Disesse (CHD) Recurrence In Patients With Pre-Existing CHD

Ran1998Enrolled8,600Registered outcomes13Posted comparisons0ConditionsCardiovascular Disease, Cerebrovascular Accident, Coronary Heart DiseaseArmsAtorvastatin
PMID 17084252other papers from this trial
Open the trial in the graph
5 · Its place in the literature

Who cites it

78 citing papers in PubMed, 3 syntheses or guidelines pooled it, 178 citations in OpenAlex.

  1. Pooled it
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  4. Trial
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  12. Review
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  15. Predictors of Five-Year Outcomes in Patients with Acute Coronary Syndromes.Journal of cardiovascular development and disease · 2025
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

18 more citing papers are in PubMed but not listed here.

6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

9 authors at 4 institutions in 2 countries.

Samia MoraBrigham and Women's Hospital, Boston, MA 02215, USA. smora@partners.org
Nanette K Wenger
David A Demicco
Andrei Breazna
S Matthijs Boekholdt
Benoit J Arsenault
Prakash Deedwania
John J P Kastelein
David D Waters
University of California, San Francisco · USCalifornia State University, Fresno · USPfizer (United States) · USUniversity of Amsterdam · NL

Funding

Novel Lipoproteins, Cardiometabolic Risk, and Statin TherapyK08HL094375 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI MORA, SAMIA · 2009 to 2012
$549k
NHLBI NIH HHS K08 HL094375
8 · The paper itself

Abstract

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

backgroundCardiovascular events occur among statin-treated patients, albeit at lower rates. Risk factors for this "residual risk" have not been studied comprehensively. We aimed to identify determinants of this risk above and beyond lipid-related risk factors. METHODS AND

resultsA total of 9251 coronary patients with low-density lipoprotein cholesterol <130 mg/dL randomized to double-blind atorvastatin 10 or 80 mg/d in the Treating to New Targets (TNT) study had complete on-treatment 1-year lipid data. Median follow-up was 4.9 years. The primary end point was major cardiovascular events (n=729): coronary death, nonfatal myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke. Multivariable determinants of increased risk were older age (adjusted hazard ratio [aHR], 1.13 per 1 SD [8.8 years]; 95% confidence interval [CI], 1.04-1.23), increased body mass index (aHR, 1.09; 95% CI, 1.02-1.17 per 4.5 kg/m(2)), male sex (aHR, 1.33; 95% CI, 1.07-1.65), hypertension (aHR, 1.38; 95% CI, 1.17-1.63), diabetes mellitus (aHR, 1.33; 95% CI, 1.11-1.60), baseline apolipoprotein B (aHR, 1.19; 95% CI, 1.11-1.28 per 19 mg/dL), and blood urea nitrogen (aHR, 1.10; 95% CI, 1.03-1.17 per 4.9 mg/dL), in addition to current smoking, prior cardiovascular disease, and calcium channel blocker use. Determinants of decreased risk were high-dose statin (aHR, 0.82; 95% CI, 0.70-0.94), aspirin use (aHR, 0.67; 95% CI, 0.56-0.81), and baseline apolipoprotein A-I (aHR, 0.91; 95% CI, 0.84-0.99 per 25 mg/dL). On-treatment 1-year lipids or apolipoproteins were not additionally associated with risk in multivariable models. Known baseline variables performed moderately well in discriminating future cases from noncases (Harrell c index=0.679).

conclusionsDeterminants of residual risk in statin-treated secondary prevention patients included lipid-related and nonlipid factors such as baseline apolipoproteins, increased body mass index, smoking, hypertension, and diabetes mellitus. A multifaceted prevention approach should be underscored to address this risk. CLINICAL

trial registrationURL: http://clinicaltrials.gov. Unique identifier: NCT00327691.

Indexed as

AdultAgedAge FactorsAnticholesteremic AgentsAtorvastatinBody Mass IndexCardiopulmonary ResuscitationCholesterol, LDLDeath, Sudden, CardiacFemaleHeart ArrestHeptanoic AcidsHumansHydroxymethylglutaryl-CoA Reductase InhibitorsHypertensionMaleAnticholesteremic AgentsAtorvastatinCholesterol, LDLHeptanoic AcidsHydroxymethylglutaryl-CoA Reductase InhibitorsPyrroles

Identifiers

PMID22461416
PMCPMC3338158
OpenAlexW2026624820

What OpenQuestion 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 OpenQuestion graph.