Evidence mapPaperPMID 34531021Full record

Trial reportJournal of the American College of Cardiology2021

Side Effect Patterns in a Crossover Trial of Statin, Placebo, and No Treatment.

James P Howard, Frances A Wood, Judith A Finegold, Alexandra N Nowbar, David M Thompson, Ahran D Arnold, Christopher A Rajkumar, Susan Connolly, Jaimini Cegla, Chris Stride and 5 more

Registry-linked trialOpen access · hybridAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Journal of the American College of Cardiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT02668016. Cited by 74 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 5 pooled it
15.2field-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.

NCT02668016 phase4completed

Self-Assessment Method for Statin Side-effects Or Nocebo

Ran2016Enrolled60Registered outcomes3Posted comparisons0ConditionsAdverse Effects, Cardiovascular Diseases, HyperlipidemiasArmsAtorvastatin, Placebo
Open the trial in the graph
3 · Its place in the literature

Who cites it

74 citing papers in PubMed, 5 syntheses or guidelines pooled it, 169 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Association Between Vitamin D Supplementation and Statin-Associated Muscle Symptoms: A Systematic Review.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2022
    Pooled it
  6. Trial
  7. Trial
  8. Trial
  9. Trial
  10. Review
  11. Review
  12. Lipid lowering in coronary artery disease - not just statins.Clinical medicine (London, England) · 2026
    Review
  13. Article
  14. Review
  15. Review
  16. Observational
  17. Review
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 1 country.

James P HowardNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Frances A WoodNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Judith A FinegoldNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Alexandra N NowbarNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
David M ThompsonNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Ahran D ArnoldNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Christopher A RajkumarNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Susan ConnollyNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Jaimini CeglaLipid and Cardiovascular Risk Service, Imperial College Healthcare NHS Trust, London, United Kingdom.
Chris StrideManagement School, University of Sheffield, Sheffield, United Kingdom.
Peter SeverNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Christine NortonDivision of Care for Long Term Conditions, King's College London, London, United Kingdom.
Simon A M ThomNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Matthew J Shun-ShinNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Darrel P FrancisNational Heart and Lung Institute, Imperial College London, London, United Kingdom. Electronic address: d.francis@imperial.ac.uk.
Imperial College London · GBImperial College Healthcare NHS Trust · GBKing's College London · GBUniversity of Sheffield · GB

Funding

British Heart Foundation FS/14/25/30676British Heart Foundation FS/14/27/30752British Heart Foundation PG/15/7/31235Department of HealthMedical Research Council MR/S021108/1Wellcome Trust 212183/Z/18/Z
6 · The paper itself

Abstract

backgroundMost people who begin statins abandon them, most commonly because of side effects.

objectivesThe purpose of this study was to assess daily symptom scores on statin, placebo, and no treatment in participants who had abandoned statins.

methodsParticipants received 12 1-month medication bottles, 4 containing atorvastatin 20 mg, 4 placebo, and 4 empty. We measured daily symptom intensity for each using an app (scale 1-100). We also measured the "nocebo" ratio: the ratio of symptoms induced by taking statin that was also induced by taking placebo.

resultsA total of 60 participants were randomized and 49 completed the 12-month protocol. Mean symptom score was 8.0 (95% CI: 4.7-11.3) in no-tablet months. It was higher in statin months (16.3; 95% CI: 13.0-19.6; P < 0.001), but also in placebo months (15.4; 95% CI: 12.1-18.7; P < 0.001), with no difference between the 2 (P = 0.388). The corresponding nocebo ratio was 0.90. In the individual-patient daily data, neither symptom intensity on starting (OR: 1.02; 95% CI: 0.98-1.06; P = 0.28) nor extent of symptom relief on stopping (OR: 1.01; 95% CI: 0.98-1.05; P = 0.48) distinguished between statin and placebo. Stopping was no more frequent for statin than placebo (P = 0.173), and subsequent symptom relief was similar between statin and placebo. At 6 months after the trial, 30 of 60 (50%) participants were back taking statins.

conclusionsThe majority of symptoms caused by statin tablets were nocebo. Clinicians should not interpret symptom intensity or timing of symptom onset or offset (on starting or stopping statin tablets) as indicating pharmacological causation, because the pattern is identical for placebo. (Self-Assessment Method for Statin Side-effects Or Nocebo [SAMSON]; NCT02668016).

Indexed as

AgedAtorvastatinCross-Over StudiesDouble-Blind MethodFemaleHumansHydroxymethylglutaryl-CoA Reductase InhibitorsMaleMiddle AgedNocebo EffectAtorvastatinHydroxymethylglutaryl-CoA Reductase Inhibitorscrossover trialdrug intolerancenoceboside effectsstatins

Identifiers

PMID34531021
PMCPMC8453640
OpenAlexW3200521827

What Socratic holds

Textmetadata
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.