Evidence map›Paper›PMID 16003294›Full record

Trial reportClinical pharmacology and therapeutics2005

High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial.

Hannu Päivä, Karin M Thelen, Rudy Van Coster, Joél Smet, Boel De Paepe, Kari M Mattila, Juha Laakso, Terho Lehtimäki, Klaus von Bergmann, Dieter Lütjohann and 1 more

2 registry-linked trialsAbstract readClinical TrialComparative StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Clinical pharmacology and therapeutics, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 92 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 5 pooled it
19.7field-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.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · 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.

NCT03696940 phase3unknown statusstarted 2018, after this paper: background citation

Estudio clínico Fase III Para Evaluar la Eficacia terapéutica en Pacientes Mexicanos Con Dislipidemia Mediante el Uso vía Oral de L-Carnitina + Atorvastatina Comparado Con Atorvastatina

Ran2018Enrolled120Registered outcomes6Posted comparisons0ConditionsCardiovascular Risk Factor, DyslipidemiasArmsAtorvastatin 10mg, L-Carnitine 500Mg Oral Tablet + Atorvastatin 10 mg
Open the trial in the graph
NCT06841536 nacompletedstarted 2025, after this paper: background citation

Combined Effects of Statins and Exercise on Physiological Health Markers and Quality of Life in Patients With Dyslipidaemia

Ran2025Enrolled120Registered outcomes61Posted comparisons0ConditionsDyslipidemiasArmsAtorvastatin 80mg, Exercise
Open the trial in the graph
3 · Its place in the literature

Who cites it

92 citing papers in PubMed, 5 syntheses or guidelines pooled it, 307 citations in OpenAlex.

  1. Pooled it
  2. Effect of atorvastatin on testosterone levels.The Cochrane database of systematic reviews · 2021
    Pooled it
  3. Pooled it
  4. Pooled it
  5. Lipid-lowering efficacy of atorvastatin.The Cochrane database of systematic reviews · 2015 · on this map
    Pooled it
  6. Trial
  7. Trial
  8. Trial
  9. Evidence for metabolic aberrations in asymptomatic persons with type 2 diabetes after initiation of simvastatin therapy.Translational research : the journal of laboratory and clinical medicine · 2015
    Trial
  10. Simvastatin impairs exercise training adaptations.Journal of the American College of Cardiology · 2013 · on this map
    Trial
  11. Trial
  12. Effect of pravastatin on plasma sterols and oxysterols in men.European journal of clinical pharmacology · 2006
    Trial
  13. Trial
  14. Article
  15. Article
  16. Article
  17. Intermuscular Adipose Tissue in CKD: A Window into Muscle Quality and Health?Clinical journal of the American Society of Nephrology : CJASN · 2025
    Review
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 3 countries.

Hannu PäiväDepartment of Internal Medicine, University Hospital of Tampere, Finland.
Karin M Thelen
Rudy Van Coster
Joél Smet
Boel De Paepe
Kari M Mattila
Juha Laakso
Terho Lehtimäki
Klaus von Bergmann
Dieter Lütjohann
Reijo Laaksonen
University of Helsinki · FITampere University Hospital · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMyopathy, probably caused by 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibition in skeletal muscle, rarely occurs in patients taking statins. This study was designed to assess the effect of high-dose statin treatment on cholesterol and ubiquinone metabolism and mitochondrial function in human skeletal muscle.

methodsForty-eight patients with hypercholesterolemia (33 men and 15 women) were randomly assigned to receive 80 mg/d of simvastatin (n = 16), 40 mg/d of atorvastatin (n = 16), or placebo (n = 16) for 8 weeks. Plasma samples and muscle biopsy specimens were obtained at baseline and at the end of the follow-up.

resultsThe ratio of plasma lathosterol to cholesterol, a marker of endogenous cholesterol synthesis, decreased significantly by 66% in both statin groups. Muscle campesterol concentrations increased from 21.1 +/- 7.1 nmol/g to 41.2 +/- 27.0 nmol/g in the simvastatin group and from 22.6 +/- 8.6 nmol/g to 40.0 +/- 18.7 nmol/g in the atorvastatin group (P = .005, repeated-measurements ANOVA). The muscle ubiquinone concentration was reduced significantly from 39.7 +/- 13.6 nmol/g to 26.4 +/- 7.9 nmol/g (P = .031, repeated-measurements ANOVA) in the simvastatin group, but no reduction was observed in the atorvastatin or placebo group. Respiratory chain enzyme activities were assessed in 6 patients taking simvastatin with markedly reduced muscle ubiquinone and in matched subjects selected from the atorvastatin (n = 6) and placebo (n = 6) groups. Respiratory chain enzyme and citrate synthase activities were reduced in the patients taking simvastatin.

conclusionsHigh-dose statin treatment leads to changes in the skeletal muscle sterol metabolism. Furthermore, aggressive statin treatment may affect mitochondrial volume.

Indexed as

AdultAgedAge FactorsAtorvastatinBiopsyCholesterolCholesterol, HDLCholesterol, LDLCitrate (si)-SynthaseDose-Response Relationship, DrugDouble-Blind MethodElectron TransportFemaleHeptanoic AcidsHumansHydroxymethylglutaryl-CoA Reductase InhibitorsAtorvastatincampesterolCholesterolCholesterol, HDLCholesterol, LDLCitrate (si)-SynthaseHeptanoic AcidsHydroxymethylglutaryl-CoA Reductase InhibitorslathosterolPhytosterolsPyrrolesSimvastatinSitosterolsSuccinate Cytochrome c OxidoreductaseUbiquinone

Identifiers

PMID16003294
OpenAlexW1988188106

What OpenQuestion holds

Textmetadata
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.