SynthesisBMC medicine2014

Unintended effects of statins from observational studies in the general population: systematic review and meta-analysis.

Ana Filipa Macedo, Fiona Claire Taylor, Juan P Casas, Alma Adler, David Prieto-Merino, Shah Ebrahim

2 registry-linked trialsOpen access · goldFull text readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in BMC medicine, 2014. The graph read 4 numbers from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. It also reports an association that does not count as treatment evidence, such as OR 0.74 (0.62 to 0.87) for quality of life & behaviour. It is linked to 2 registered trials, which are not on this map. Cited by 77 papers, 8 of them syntheses that pooled it.

4numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 8 pooled it
23.8field-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

Quality of life & behaviouran association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
OR 0.970.88 to 1.05
Statins were associated with lower risks of dementia and cognitive impairment, venous thrombo-embolism, fractures and pneumonia, but these findings were attenuated in analyses restricted to higher quality studies (respectively: OR 0.74 (95% CI 0.62 to 0.87); OR 0.92 (95% CI 0.81 to 1.03); OR 0.97 (95% CI 0.88 to 1.05); OR 0.92 (95% CI 0.83 to 1.02)); and marked heterogeneity of effects across studies remained.
Quality of life & behaviouran association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
OR 0.920.81 to 1.03
Statins were associated with lower risks of dementia and cognitive impairment, venous thrombo-embolism, fractures and pneumonia, but these findings were attenuated in analyses restricted to higher quality studies (respectively: OR 0.74 (95% CI 0.62 to 0.87); OR 0.92 (95% CI 0.81 to 1.03); OR 0.97 (95% CI 0.88 to 1.05); OR 0.92 (95% CI 0.83 to 1.02)); and marked heterogeneity of effects across studies remained.
Quality of life & behaviouran association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
OR 0.740.62 to 0.87
Statins were associated with lower risks of dementia and cognitive impairment, venous thrombo-embolism, fractures and pneumonia, but these findings were attenuated in analyses restricted to higher quality studies (respectively: OR 0.74 (95% CI 0.62 to 0.87); OR 0.92 (95% CI 0.81 to 1.03); OR 0.97 (95% CI 0.88 to 1.05); OR 0.92 (95% CI 0.83 to 1.02)); and marked heterogeneity of effects across studies remained.
Quality of life & behaviouran association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
OR 0.920.83 to 1.02
Statins were associated with lower risks of dementia and cognitive impairment, venous thrombo-embolism, fractures and pneumonia, but these findings were attenuated in analyses restricted to higher quality studies (respectively: OR 0.74 (95% CI 0.62 to 0.87); OR 0.92 (95% CI 0.81 to 1.03); OR 0.97 (95% CI 0.88 to 1.05); OR 0.92 (95% CI 0.83 to 1.02)); and marked heterogeneity of effects across studies remained.

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×quality of life & behaviour

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

3 readable studies in this cell: 0 favour the treatment, 2 find no difference, 1 favour the comparator.

Belief with this paper
0.25no deciding trial · 0 families support, 0 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
1 · no effect

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.

NCT05072275 unknown statusnot on this mapstarted 2023, after this paper: background citation

Prospective Electronic Polygenic Risk Study (PEPRS) - First Phase

TypeobservationalSponsorScripps Translational Science InstituteRan2023 to 2023Enrolled1,000ConditionsCoronary Artery Disease
NCT05175651 nanot yet recruitingnot on this mapstarted 2023, after this paper: background citation

Prospective Electronic Polygenic Risk Study - Second Phase

TypeinterventionalSponsorScripps Translational Science InstituteRan2023 to 2027Enrolled10,000ConditionsCoronary Artery Disease, GlaucomaArmsGenetic risk assessment
5 · Its place in the literature

Who cites it

77 citing papers in PubMed, 8 syntheses or guidelines pooled it, 183 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Trial
  10. Trial
  11. Trial
  12. Trial
  13. Trial
  14. Observational
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article

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

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 3 institutions in 1 country.

Ana Filipa MacedoCochrane Heart Group, London School of Hygiene and Tropical Medicine, London, UK. filipa_macedopt@hotmail.com.
Fiona Claire Taylor
Juan P Casas
Alma Adler
David Prieto-Merino
Shah Ebrahim
London School of Hygiene & Tropical Medicine · GBCochrane · GBUniversity College London · GB

Funding

British Heart Foundation PG/09/022/26739
8 · The paper itself

Abstract

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

backgroundEfficacy of statins has been extensively studied, with much less information reported on their unintended effects. Evidence from randomized controlled trials (RCTs) on unintended effects is often insufficient to support hypotheses generated from observational studies. We aimed to systematically assess unintended effects of statins from observational studies in general populations with comparison of the findings where possible with those derived from randomized trials.

methodsMedline (1998 to January 2012, week 3) and Embase (1998 to 2012, week 6) were searched using the standard BMJ Cohort studies filter. The search was supplemented with reference lists of all identified studies and contact with experts in the field. We included prospective studies with a sample size larger than 1,000 participants, case control (of any size) and routine health service linkage studies of over at least one year duration. Studies in subgroups of patients or follow-up of patient case series were excluded, as well as hospital-based cohort studies.

resultsNinety studies were identified, reporting on 48 different unintended effects. Statins were associated with lower risks of dementia and cognitive impairment, venous thrombo-embolism, fractures and pneumonia, but these findings were attenuated in analyses restricted to higher quality studies (respectively: OR 0.74 (95% CI 0.62 to 0.87); OR 0.92 (95% CI 0.81 to 1.03); OR 0.97 (95% CI 0.88 to 1.05); OR 0.92 (95% CI 0.83 to 1.02)); and marked heterogeneity of effects across studies remained. Statin use was not related to any increased risk of depression, common eye diseases, renal disorders or arthritis. There was evidence of an increased risk of myopathy, raised liver enzymes and diabetes (respectively: OR 2.63 (95% CI 1.50 to 4.61); OR 1.54 (95% CI 1.47 to 1.62); OR 1.31 (95% CI 0.99 to 1.73)).

conclusionsOur systematic review and meta-analyses indicate that high quality observational data can provide relevant evidence on unintended effects of statins to add to the evidence from RCTs. The absolute excess risk of the observed harmful unintended effects of statins is very small compared to the beneficial effects of statins on major cardiovascular events.

Indexed as

Observational Studies as TopicPopulation SurveillanceDementiaDiabetes MellitusHumansHydroxymethylglutaryl-CoA Reductase InhibitorsRandomized Controlled Trials as TopicTreatment OutcomeHydroxymethylglutaryl-CoA Reductase Inhibitors

Identifiers

PMID24655568
PMCPMC3998050
OpenAlexW2070410095

What Socratic holds

Textfull text, public
LicenceCC BY
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.