Trial reportCirculation. Cardiovascular genetics2008

Pharmacogenetic predictors of statin-mediated low-density lipoprotein cholesterol reduction and dose response.

Deepak Voora, Svati H Shah, Carol R Reed, Jun Zhai, David R Crosslin, Chad Messer, Benjamin A Salisbury, Geoffrey S Ginsburg

Open access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Circulation. Cardiovascular genetics, 2008. The graph read 1 number from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. Cited by 30 papers, 4 of them syntheses that pooled it.

1number the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 4 pooled it
6.1field-weighted citation impact, top 4% 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 · dyslipidemiafeeds one cell of the map
reduction -1.50P=0.0001
Twenty-six subjects carried the minor allele of rs12003906, which was associated with an attenuated LDLc reduction (LDLc reduction in carriers versus noncarriers -24.1+/-2.6% versus -32.2+/-1.5%; P=0.0001).

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.

Investigational compounds×lipids

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

9 readable studies in this cell: 4 favour the treatment, 3 find no difference, 2 favour the comparator.

Belief with this paper
0.50contested · 4 families support, 4 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT004798822,414 enrolled · 2007
Δ 2.401.30 to 3.40
NCT002899002,340 enrolled · 2006
Δ -13.2-16.8 to -9.60
NCT01105975398 enrolled · 2010
Δ 56.743.6 to 69.8
NCT01218204287 enrolled · 2010
Δ -6.10-23.5 to 11.3
NCT04992065267 enrolled · 2021
Δ -31.9-43.0 to -20.9
NCT01375075165 enrolled · 2011
Δ 74.253.4 to 95.1
NCT00868790118 enrolled · 2009
Δ -0.80-4.60 to 3.10
NCT0134221193 enrolled · 2011
Δ -5.63-25.1 to 13.8
NCT0220216170 enrolled · 2014
Δ 1.030.91 to 1.17

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

5 · Its place in the literature

Who cites it

30 citing papers in PubMed, 4 syntheses or guidelines pooled it, 87 citations in OpenAlex.

  1. Pooled it
  2. Lipid-lowering efficacy of atorvastatin.The Cochrane database of systematic reviews · 2015 · on this map
    Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. The SLCO1B1*5 genetic variant is associated with statin-induced side effects.Journal of the American College of Cardiology · 2009
    Trial
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Role of Genetic Variations in the Hepatic Handling of Drugs.International journal of molecular sciences · 2020 · on this map
    Review
  17. Article
  18. Article
  19. Review
  20. Review
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

8 authors at 1 institution in 1 country.

Deepak VooraDivision of Cardiovascular Medicine, the Institute for Genome & Science Policy, and the Center for Human Genetics, Duke University, Durham, NC 27708, USA.
Svati H Shah
Carol R Reed
Jun Zhai
David R Crosslin
Chad Messer
Benjamin A Salisbury
Geoffrey S Ginsburg
MaineHealth · US

Funding

MULTIDISCIPLINARY HEART &VASCULAR DISEASEST32HL007101 · DUKE UNIVERSITY · 1985 to 2005
$2.5M
NHLBI NIH HHS T32 HL007101
8 · The paper itself

Abstract

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

backgroundThere is interindividual variation in low-density lipoprotein cholesterol (LDLc) lowering by statins and limited study into the genetic associations of the dose dependant LDLc lowering by statins. METHODS AND

resultsFive hundred nine patients with hyperlipidemia were randomly assigned atorvastatin 10 mg, simvastatin 20 mg, or pravastatin 10 mg (low-dose phase) followed by 80 mg, 80 mg, and 40 mg (high-dose phase), respectively. Thirty-one genes in statin, cholesterol, and lipoprotein metabolism were sequenced and 489 single nucleotide polymorphisms with minor allele frequencies >2% were tested for associations with percentage LDLc lowering at low doses using multivariable adjusted general linear regression. Significant associations from the analysis at low dose were then repeated at high-dose statins. At low doses, only 1 single nucleotide polymorphism met our experiment-wide significance level, ABCA1 rs12003906. Twenty-six subjects carried the minor allele of rs12003906, which was associated with an attenuated LDLc reduction (LDLc reduction in carriers versus noncarriers -24.1+/-2.6% versus -32.2+/-1.5%; P=0.0001). In addition, we replicated the association with the APOE epsilon3 allele and a reduced LDLc reduction. At high doses, carriers of the minor allele of ABCA1 rs12003906 and the APOE epsilon3 allele improved their LDLc reduction but continued to have a diminished LDLc reduction compared with noncarriers (-30.5+/-4.0% versus -42.0+/-2.4%; P=0.005) and (-38.5+/-1.9% versus -45.3+/-2.8%; P=0.009), respectively.

conclusionsAn intronic single nucleotide polymorphism in ABCA1 and the APOE epsilon3 allele are associated with reduced LDLc lowering by statins and identify individuals who may be resistant to maximal LDLc lowering by statins.

Indexed as

AdolescentAdultAgedAllelesAnticholesteremic AgentsApolipoprotein E3AtorvastatinATP Binding Cassette Transporter 1ATP-Binding Cassette TransportersCholesterol, LDLDose-Response Relationship, DrugFemaleGene FrequencyGenetic Predisposition to DiseaseGenotypeHaplotypesABCA1 protein, humanAnticholesteremic AgentsApolipoprotein E3AtorvastatinATP Binding Cassette Transporter 1ATP-Binding Cassette TransportersCholesterol, LDLHeptanoic AcidsHydroxymethylglutaryl-CoA Reductase InhibitorsPravastatinPyrrolesSimvastatin

Identifiers

PMID20031551
PMCPMC2995295
OpenAlexW2112014040

What Socratic holds

Texttitle and abstract
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.