SynthesisBritish journal of clinical pharmacology2017

Effect of ezetimibe on plasma adipokines: a systematic review and meta-analysis.

Eva Dolezelova, Evan Stein, Giuseppe Derosa, Pamela Maffioli, Petr Nachtigal, Amirhossein Sahebkar

Open access · bronzeAbstract readComparative StudyMeta-AnalysisSystematic Review
In one paragraph

Synthesis in British journal of clinical pharmacology, 2017. The graph read 5 numbers from its abstract, feeding 2 cells of the map, but none could be read as for or against, so it casts no vote. Cited by 10 papers, 3 of them syntheses that pooled it.

5numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 3 pooled it
2.5field-weighted citation impact, top 12% 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

Plasma concentrations of leptinezetimibe/statin combination therapy vs statin monotherapycomparator not stated · ascvdfeeds 2 cells of the map
Δ -0.75-2.35 to 0.85comparison_kind
RESULTS: Meta-analysis of 23 controlled trials did not suggest any significant effect of adding ezetimibe on top of statin therapy on plasma concentrations of adiponectin (SMD 0.34, 95% CI -0.28, 0.96; P = 0.288), leptin (SMD -0.75, 95% CI: -2.35, 0.85; P = 0.360), plasminogen activator inhibitor 1 (SMD -1.06, 95% CI: -2.81, 0.69; P = 0.236) and interleukin 6 (SMD 0.30, 95% CI: -0.08, 0.67; P = 0.124).
Plasma concentrations of adiponectinezetimibe/statin combination therapy vs statin monotherapycomparator not stated · ascvdfeeds 2 cells of the map
Δ 0.34-0.28 to 0.96comparison_kind
RESULTS: Meta-analysis of 23 controlled trials did not suggest any significant effect of adding ezetimibe on top of statin therapy on plasma concentrations of adiponectin (SMD 0.34, 95% CI -0.28, 0.96; P = 0.288), leptin (SMD -0.75, 95% CI: -2.35, 0.85; P = 0.360), plasminogen activator inhibitor 1 (SMD -1.06, 95% CI: -2.81, 0.69; P = 0.236) and interleukin 6 (SMD 0.30, 95% CI: -0.08, 0.67; P = 0.124).
Plasma concentrations of tumour necrosis factor α (TNF-α)ezetimibe/statin combination therapy vs statin monotherapycomparator not stated · ascvdfeeds 2 cells of the map
Δ -0.48-0.87 to -0.08comparison_kind
However, significantly greater reductions in plasma concentrations of tumour necrosis factor α (TNF-α) (SMD -0.48, 95% CI -0.87, -0.08; P = 0.018) were achieved with ezetimibe/statin combination therapy.
Plasma concentrations of interleukin 6ezetimibe/statin combination therapy vs statin monotherapycomparator not stated · ascvdfeeds 2 cells of the map
Δ 0.30-0.08 to 0.67comparison_kind
RESULTS: Meta-analysis of 23 controlled trials did not suggest any significant effect of adding ezetimibe on top of statin therapy on plasma concentrations of adiponectin (SMD 0.34, 95% CI -0.28, 0.96; P = 0.288), leptin (SMD -0.75, 95% CI: -2.35, 0.85; P = 0.360), plasminogen activator inhibitor 1 (SMD -1.06, 95% CI: -2.81, 0.69; P = 0.236) and interleukin 6 (SMD 0.30, 95% CI: -0.08, 0.67; P = 0.124).
Plasma concentrations of plasminogen activator inhibitor 1ezetimibe/statin combination therapy vs statin monotherapycomparator not stated · ascvdfeeds 2 cells of the map
Δ -1.06-2.81 to 0.69comparison_kind
RESULTS: Meta-analysis of 23 controlled trials did not suggest any significant effect of adding ezetimibe on top of statin therapy on plasma concentrations of adiponectin (SMD 0.34, 95% CI -0.28, 0.96; P = 0.288), leptin (SMD -0.75, 95% CI: -2.35, 0.85; P = 0.360), plasminogen activator inhibitor 1 (SMD -1.06, 95% CI: -2.81, 0.69; P = 0.236) and interleukin 6 (SMD 0.30, 95% CI: -0.08, 0.67; P = 0.124).

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×pharmacokinetics & dosing

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

1 readable study in this cell: 1 favour the treatment, 0 find no difference, 0 favour the comparator.

Belief with this paper
0.50one trial · 1 family supports, 0 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
NCT0086326522 enrolled · 2009
Δ 22.8

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

Statins×pharmacokinetics & dosing

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

2 readable studies in this cell: 0 favour the treatment, 2 find no difference, 0 favour the comparator.

Belief with this paper
0.00contested · 0 families support, 1 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
NCT00943124220 enrolled · 2007
Least-Squares Mean Ratio 0.970.93 to 1.00

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

10 citing papers in PubMed, 3 syntheses or guidelines pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Effect of ezetimibe on plasma adipokines: a systematic review and meta-analysis.British journal of clinical pharmacology · 2017 · on this map
    Pooled it
  4. Trial
  5. Trial
  6. Review
  7. Review
  8. Article
  9. Article
  10. 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

6 authors at 4 institutions in 5 countries.

Eva DolezelovaFaculty of Pharmacy in Hradec Kralove, Department of Biological and Medical Sciences, Charles University, Hradec Kralove, Czech Republic.
Evan SteinMetabolic and Atherosclerosis Research Center, Cincinnati, OH, USA.
Giuseppe DerosaCentre of Diabetes and Metabolic Diseases, Department of Internal Medicine and Therapeutics, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.ORCID 0000-0003-3573-4760
Pamela MaffioliCentre of Diabetes and Metabolic Diseases, Department of Internal Medicine and Therapeutics, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Petr NachtigalFaculty of Pharmacy in Hradec Kralove, Department of Biological and Medical Sciences, Charles University, Hradec Kralove, Czech Republic.
Amirhossein SahebkarBiotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Charles University · CZUniversity of Pavia · ITLouisville Metabolic and Atherosclerosis Research Center · USMashhad University of Medical Sciences · IR

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

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

aimsStatins are known to influence the status of adipokines, which play a key role in the pathophysiology of cardiometabolic diseases. As the effect of ezetimibe as an add-on to statin therapy on the impact of statins on plasma adipokines levels is currently unclear, the aim of the present study was to investigate this through a meta-analysis of controlled trials.

methodsA systematic review was performed, followed by a bibliographic search in PubMed, Medline, SCOPUS, Web of Science and Google Scholar databases. Quantitative data synthesis was performed using a fixed- or random-effects model (based on the level of interstudy heterogeneity) and the generic inverse variance weighting method. Effect sizes were expressed as standardized mean difference (SMD) and 95% confidence interval (CI).

resultsMeta-analysis of 23 controlled trials did not suggest any significant effect of adding ezetimibe on top of statin therapy on plasma concentrations of adiponectin (SMD 0.34, 95% CI -0.28, 0.96; P = 0.288), leptin (SMD -0.75, 95% CI: -2.35, 0.85; P = 0.360), plasminogen activator inhibitor 1 (SMD -1.06, 95% CI: -2.81, 0.69; P = 0.236) and interleukin 6 (SMD 0.30, 95% CI: -0.08, 0.67; P = 0.124). However, significantly greater reductions in plasma concentrations of tumour necrosis factor α (TNF-α) (SMD -0.48, 95% CI -0.87, -0.08; P = 0.018) were achieved with ezetimibe/statin combination therapy.

conclusionsThe results suggested that ezetimibe add-on to statin therapy is associated with an enhanced TNF-α-lowering effect compared with statin monotherapy. Owing to the emerging role of TNF-α in the pathogenesis of metabolic disorders, further investigations are required to unveil the translational relevance of this TNF-α-lowering effect.

Indexed as

AdiponectinAnticholesteremic AgentsAtherosclerosisDrug Therapy, CombinationEzetimibeHumansHydroxymethylglutaryl-CoA Reductase InhibitorsInterleukin-6LeptinPlasminogen Activator Inhibitor 1Randomized Controlled Trials as TopicTumor Necrosis Factor-alphaAdiponectinADIPOQ protein, humanAnticholesteremic AgentsEzetimibeHydroxymethylglutaryl-CoA Reductase InhibitorsIL6 protein, humanInterleukin-6LeptinPlasminogen Activator Inhibitor 1SERPINE1 protein, humanTumor Necrosis Factor-alphaadipose tissuecytokineezetimibepleiotropicstatintumour necrosis factor α

Identifiers

PMID28166606
PMCPMC5465335
OpenAlexW2586160953

What Socratic holds

Texttitle and abstract
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.