SynthesisPloS one2025

Safety outcomes of statin vs non-statin lipid-lowering interventions in patients with prior statin-associated muscle symptoms: A systematic review and meta-analysis.

Philipp Stefan Aebi, Fanny Villoz, Jonas Bührer, Christina Lyko, Nazanin Abolhassani, Cinzia Del Giovane, Baris Gencer, Nicolas Rodondi, Manuel R Blum

Abstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in PloS one, 2025. 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. Not yet cited in PubMed.

1number the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
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

Adverse events & safetycomparator not stated · ascvd, dyslipidemiafeeds one cell of the map
OR 1.481.03 to 2.12
Therapy discontinuation due to muscle symptoms in RCTs was higher in the statin-based than the comparator groups (OR 1.48, 95%CI 1.03-2.12, I2 = 17.6%).

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×adverse events & safety

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

11 readable studies in this cell: 3 favour the treatment, 7 find no difference, 1 favour the comparator.

Belief with this paper
0.16contested · 1 family supports, 4 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
NCT002899002,340 enrolled · 2006
Δ 13.79.40 to 18.0
NCT01294683977 enrolled · 2011
Δ -1.03-7.30 to 5.25
NCT00728988499 enrolled · 2008
Δ 1.00-7.30 to 9.30
NCT01678820299 enrolled · 2012
Δ -0.40-10.2 to 9.30

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Philipp Stefan AebiInstitute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.ORCID https://orcid.org/0009-0000-2034-9793
Fanny VillozInstitute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
Jonas BührerInstitute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
Christina LykoCentre médico-chirurgical de l'obésité, HÔPITAL RIVIERA-CHABLAIS, Route des Tilles 6A, Rennaz, Switzerland.
Nazanin AbolhassaniInstitute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
Cinzia Del GiovaneInstitute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
Baris GencerInstitute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
Nicolas RodondiInstitute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
Manuel R BlumInstitute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.

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.

backgroundStatin-associated muscle symptoms (SAMS) are an obstacle in the prevention of cardiovascular events. A systematic assessment of the evidence of interventions in the setting of SAMS is lacking.

objectiveTo assess the evidence of strategies of statin-based vs non-statin based therapies in patients with a history of SAMS.

methodsMEDLINE, EMBASE, Cochrane Central Register of Controlled Clinical Trials, Scopus, Clinicaltrials.gov and Proquest databases were searched from inception up to February 2024.We included randomized controlled trials (RCTs) and non-randomized studies involving patients with history of prior SAMS, comparing statin-based therapy to a comparator. We followed the PRISMA guideline with multiple authors involved at each stage. A random-effect model was used in the meta-analysis. We defined the primary outcome as incidence of muscle symptoms. The secondary outcomes were proportion of statin discontinuation of statin-based therapy within patients with history of SAMS. The protocol was registered on PROSPERO (CRD42020202619).

resultsIn 23 studies (13 RCTs, 2 prospective and 8 retrospective studies) there were in total 1868 participants in RCTs and 47'628 participants in non-RCTs (follow-up 12 weeks - 31 months). Our confidence in the body of evidence using GRADE was moderate for the primary outcome and low-moderate for the secondary outcome. In RCTs among patients with history of SAMS, there was high heterogeneity in the statin regimens and controls (placebo/non-daily dosing/ezetimibe/PCSK9 inhibitors). In RCTs, the meta-analysis showed no difference between statin-based and control groups in the incidence of muscle symptoms (OR 1.19, 95%CI 0.86-1.64, I2: 46.3%)). Therapy discontinuation due to muscle symptoms in RCTs was higher in the statin-based than the comparator groups (OR 1.48, 95%CI 1.03-2.12, I2 = 17.6%).

conclusionOur findings suggest that patients with a history of SAMS can be re-challenged with statins. More high-quality evidence is needed to strengthen guidelines regarding the management of SAMS.

Indexed as

Hydroxymethylglutaryl-CoA Reductase InhibitorsHypolipidemic AgentsMuscular DiseasesCardiovascular DiseasesHumansRandomized Controlled Trials as TopicHydroxymethylglutaryl-CoA Reductase InhibitorsHypolipidemic Agents

Identifiers

PMID41379822
PMCPMC12698018

What Socratic holds

Texttitle and abstract
LicenceCC BY
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.