Financiado en parte por Abbott Laboratories, Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, Sanofi, Biogen, CSL Behring, Regeneron Pharmaceuticals, Medicines Company, Singulex, Amryt Pharma, Moderna, Zora Biosciences, Abiomed, ARCA Biopharma, Daiichi-Sankyo, Novo Nordisk, Silence Therapeutics, Esperion Therapeutics, American Regent, Janssen Research and Development
Assessment of adverse effects attributed to statin therapy in product labels: a meta-analysis of double-blind randomised controlled trials
Cholesterol Treatment Trialists' (CTT) Collaboration. Electronic address: ctt@ndph.ox.ac.uk, Cholesterol Treatment Trialists' (CTT) Collaboration
Lancet (London, England) · 35 citas
Etiquetas de revisión
Financiado por la industriaDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Metaanálisis (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiado por la industria
- Organización sin fines de lucro
- Bill and Melinda Gates Foundation
- Empresa
- Abbott Laboratories
- Empresa
- Amgen
- Empresa
- Bristol-Myers Squibb
- Empresa
- Eli Lilly and Company
- Empresa
- Pfizer
- Empresa
- AstraZeneca
- Empresa
- Sanofi
- Universidad u hospital
- Brigham and Women's Hospital
- Empresa
- Biogen
- Empresa
- CSL Behring
- Universidad u hospital
- Queen Mary University of London
- Gobierno
- Japan Agency for Medical Research and Development
- Universidad u hospital
- South Australian Health and Medical Research Institute
- Empresa
- Regeneron Pharmaceuticals
- Gobierno
- National Institute for Health and Care Excellence
- Empresa
- Medicines Company
- Empresa
- Singulex
- Empresa
- Amryt Pharma
- Empresa
- Moderna
- Empresa
- Zora Biosciences
- Empresa
- Abiomed
- Empresa
- ARCA Biopharma
- Gobierno
- National Institute for Health and Care Research
- Organización sin fines de lucro
- British Heart Foundation
- Organización sin fines de lucro
- Diabetes UK
- Universidad u hospital
- University of Oxford
- Organización sin fines de lucro
- European Society of Cardiology
- Gobierno
- Ministry of Education, Culture, Sports, Science and Technology
- Empresa
- Daiichi-Sankyo
- Empresa
- Novo Nordisk
- Organización sin fines de lucro
- Nakatani Foundation for Advancement of Measuring Technologies in Biomedical Engineering
- Empresa
- Silence Therapeutics
- Empresa
- Esperion Therapeutics
- Gobierno
- National Institutes of Health
- Empresa
- American Regent
- Gobierno
- Medical Research Council
- Gobierno
- National Health and Medical Research Council
- Gobierno
- Japan Society for the Promotion of Science
- Gobierno
- NIHR Oxford Biomedical Research Centre
- Empresa
- Janssen Research and Development
- Gobierno
- UKRI Medical Research Council
- Gobierno
- National Institute for Health Research (NIHR)
- Subvenciones
- Japan Agency for Medical Research and Development (A447TR); British Heart Foundation (CH/1996001/9454); Japan Society for the Promotion of Science (19H03661); National Institute for Health and Care Research (17/140/02); Ministry of Education, Culture, Sports, Science and Technology (19H03661); National Health and Medical Research Council (1150467); British Heart Foundation (PG/18/16/33570); National Health and Medical Research Council (2009800); National Health and Medical Research Council (1037786); Japan Agency for Medical Research and Development (A368TS); Medical Research Council (MC_UU_00017/4); National Health and Medical Research Council (2018537); Nakatani Foundation for Advancement of Measuring Technologies in Biomedical Engineering (19H03661)
Según 43 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2026-02-01 · Lancet · vol. 407 · número 10529 · págs. 689–703
- Editorial
- Elsevier BV
- Citado
- 42 citas · más que el 100% de estudios similares · 112.1× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 67 trabajos
- Acceso
- Acceso abierto (revista híbrida) · CC-BY
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Pharmacovigilance and Adverse Drug Reactions · Statistical Methods in Clinical Trials
- Palabras clave
- statins, adverse drug reactions, product labels, Summary of Product Characteristics, drug safety, individual patient data, liver transaminases, liver function tests, urine composition, edema, diabetes mellitus, statin therapy, false discovery rate, atorvastatin, fluvastatin, pravastatin, rosuvastatin
- MeSH
- humans, hydroxymethylglutaryl-coa reductase inhibitors, double-blind method, drug labeling, randomized controlled trials as topic
100 autores
- Christina A. Reith
- Lisa S. Blackwell
- Jonathan Emberson
- David Preiss
- Enti Spata
- Kelly Davies
- Heather J. Halls
- Charlie Harper
- Lisa Holland
- Kate Wilson
- Robert Humphrey
- Alistair Roddick
- Christopher Paul Cannon
- Barry R. Davis
- Paul N. Durrington
- Shinya Goto
- Graham A Hitman
- G. Kees Hovingh
- Wolfgang Koenig
- Vera Krane
- Martin J Landray
- Borislava Mihaylova
- Connie B. Newman
- Jeffrey L. Probstfield
- Marc Steven Sabatine
- Naveed A. Sattar
- Gregory G. Schwartz
- Andrew Maxwell Tonkin
- Harvey Douglas White
- Jane Armitage
- Anthony Keech
- John Simes
- Rory Collins
- Colin Baigent
- Elizabeth Barnes
- Jordan Fulcher
- William Guy Herrington
- Adrienne C Kirby
- Rachel O'Connell
- Pierre Amarenco
- Hiroyuki Arashi
- Philip J. Barter
- D. J. Betteridge
- Michael A. Blazing
- Gerard J. Blauw
- Marc P. Bonaca
- Jackie Bosch
- Louise J. Bowman
- Eugene Braunwald M. D
- Richard A. Bulbulia
- Robert P. Byington
- Robert Clarke
- Michael B. Clearfield
- Stuart M. Cobbe
- Helen Martina Colhoun
- Björn Dahlöf
- James de Lemos
- John R. Downs
- Bengt Fellström
- Lawrence J. Fine
- Marcus Flather
- Ian Ford
- Maria Grazia Franzosi
- John Fuller
- Curt Daniel Furberg
- Robert J Glynn
- U. Goldbourt
- David Gordon
- Antonio M. Gotto
- Richard Grimm
- Ajay Gupta
- C Morton Hawkins
- Richard Haynes
- Hallvard Holdaas
- Jemma Hopewell
- Alan G. Jardine
- J. Wouter Jukema
- John J.P. Kastelein
- Sharon Kean
- Patricia M. Kearney
- George D. Kitas
- John Kjekshus
- Genell L. Knatterud
- Robert H. Knopp
- John Kjekshus
- Michael J. Koren
- John C. LaRosa
- Roberto Latini
- Eva Lonn
- Donata Lucci
- Jean G. MacFadyen
- P. W. Macfarlane
- Stephen W MacMahon
- Aldo Pietro Maggioni
- Roberto Marchioli
- Ian C. Marschner
- Lemuel A. Moyé
- Heather Murray
- Sabina A Murphy
- Andrew Neil
Resumen
El texto original del estudio, en el idioma en que se publicó.
Background
Statin product labels (eg, Summaries of Product Characteristics [SmPCs]) list certain adverse outcomes as potential treatment-related effects based mainly on non-randomised and non-blinded studies, which might be subject to bias. We aimed to assess the evidence for such undesirable effects more reliably through a meta-analysis of individual participant data from large double-blind trials of statin therapy.
Methods
In this meta-analysis of individual participant-level data from double-blind randomised controlled trials, we generated a list of all undesirable effect terms listed in statin SmPCs by searching an electronic medicines compendium for five statins (atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin). Randomised trials were eligible for meta-analysis of these effects if they involved at least 1000 participants, had a scheduled treatment period of at least 2 years, and involved a double-blind comparison of statin versus placebo or of a more intensive versus a less intensive statin regimen. Event rate ratios (RRs) and 95% CIs were calculated with statistical significance assessed after controlling the false discovery rate (FDR) at 5%.
Findings
19 trials compared statin versus placebo (123 940 participants, median follow-up 4·5 years [IQR 3·1-5·4]). In addition to previously reported effects on muscle outcomes and diabetes, only four of 66 further undesirable outcomes that had been attributed to statins were FDR significant: abnormal liver transaminases (783 participants [0·30% per annum] allocated statin vs 556 [0·22% per annum] allocated placebo, RR 1·41 [95% CI 1·26-1·57]) and other liver function test abnormalities (651 participants [0·25% per annum] allocated statin vs 518 [0·20% per annum] allocated placebo, RR 1·26 [1·12-1·41]; absolute annual excess of 0·13% for combined liver function test abnormality), urinary composition alteration (556 [0·21% per annum] allocated statin vs 472 [0·18% per annum] allocated placebo, RR 1·18 [1·04-1·33]), and oedema (3495 [1·38% per annum] allocated statin vs 3299 [1·31% per annum] allocated placebo, RR 1·07 [1·02-1·12]). Analysis of the four trials of more intensive versus less intensive statin regimens also found significant excesses for abnormal liver transaminases and other liver function test abnormalities (supporting a dose-dependent effect), but no significant excess was found for urinary composition alteration or oedema.
Interpretation
Adverse event data from blinded randomised trials do not support causal relationships between statin therapy and most of the conditions (including cognitive impairment, depression, sleep disturbance, and peripheral neuropathy) listed in product labels as potential undesirable effects. In light of these findings, such labelling and other official sources of health information should be revised so that patients and their doctors can make appropriately informed decisions regarding statin therapy.
Funding
British Heart Foundation, UK Medical Research Council, and Australian National Health and Medical Research Council.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).
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