Evidence map›Paper›PMID 29718253›Full record

ReviewEuropean heart journal2018

Adverse effects of statin therapy: perception vs. the evidence - focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke and cataract.

François Mach, Kausik K Ray, Olov Wiklund, Alberto Corsini, Alberico L Catapano, Eric Bruckert, Guy De Backer, Robert A Hegele, G Kees Hovingh, Terry A Jacobson and 18 more

Registry-linked trialOpen access · bronzeAbstract readComparative StudyReview
PubMed Full text at PMC Publisher
In one paragraph

Review in European heart journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06767774 (Comparison of Pitavastatin Plus Ezetimibe Versus High-Intensity Statin Therapy on Risk of New-Onset Diabetes Mellitus in Prediabetic Patients With Atherosclerotic Cardiovascular Disease), which is not on this map. Cited by 149 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
149citing papers in PubMed, 12 pooled it
43.1field-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.

NCT06767774 phase4recruitingstarted 2025, after this paper: background citation

Comparison of Pitavastatin Plus Ezetimibe Versus High-Intensity Statin Therapy on Risk of New-Onset Diabetes Mellitus in Prediabetic Patients With Atherosclerotic Cardiovascular Disease

Ran2025Enrolled2,000Registered outcomes13Posted comparisons0ConditionsASCVD, Diabetes, StatinArmsCombination therapy, High intensity statin monotherapy
PMID 29263150PMID 23704171PMID 21693744PMID 20167359PMID 10333939PMID 11270938PMID 12087009PMID 12186811PMID 17559928PMID 17601626PMID 22410123PMID 24239923other papers from this trial
Open the trial in the graph
3 · Its place in the literature

Who cites it

149 citing papers in PubMed, 12 syntheses or guidelines pooled it, 375 citations in OpenAlex.

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  10. Statins for asthma.The Cochrane database of systematic reviews · 2020
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89 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

28 authors at 20 institutions in 14 countries.

François MachDivision of Cardiology, Department of Medical Specialties, Foundation for Medical Researches, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4 1205 Geneva, Switzerland.
Kausik K RayImperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, UK.
Olov WiklundDepartment of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
Alberto CorsiniDepartment of Pharmacological and Biomolecular Sciences, University of Milan and IRCCS Multimedica, Milan, Italy.
Alberico L CatapanoDepartment of Pharmacological and Biomolecular Sciences, University of Milan and IRCCS Multimedica, Milan, Italy.
Eric BruckertNational Institute for Health and Medical Research (INSERM) UMRS1166, Department of Endocrinology-Metabolism, ICAN-Institute of CardioMetabolism and Nutrition, AP-HP, Hôpital de la Pitié, Paris, France.
Guy De BackerDepartment of Public Health, University Hospital Ghent, Ghent, Belgium.
Robert A HegeleDepartment of Medicine, Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
G Kees HovinghDepartment of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Terry A JacobsonDepartment of Medicine, Emory University, Atlanta, GA, USA.
Ronald M KraussDepartment of Atherosclerosis Research, Children's Hospital Oakland Research Institute, Oakland, CA, USA.
Ulrich LaufsDepartment of Cardiology, University of Leipzig, Leipzig, Germany.
Lawrence A LeiterLi Ka Shing Knowledge Institute of St Michael's Hospital, University of Toronto, Toronto, ON, Canada.
Winfried MärzVth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany.
Børge G NordestgaardDepartment of Clinical Biochemistry and The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
Frederick J RaalFaculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.
Michael RodenGerman Center for Diabetes Research (DZD), München-Neuherberg, Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Düsseldorf, Germany.
Raul D SantosHospital Israelita Albert Einstein, São Paulo, Brazil.
Evan A SteinMetabolic and Atherosclerosis Research Center, Cincinnati, OH, USA.
Erik S StroesDepartment of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Paul D ThompsonHartford Hospital, Hartford, CT, USA.
Lale TokgözogluDepartment of Cardiology, Hacettepe University, Ankara, Turkey.
Georgirene D VladutiuJacobs School of Medicine & Biomedical Sciences, University at Buffalo, The State University of New York, New York, USA.
Baris GencerDivision of Cardiology, Department of Medical Specialties, Foundation for Medical Researches, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4 1205 Geneva, Switzerland.
Jane K StockEuropean Atherosclerosis Society, Gothenburg, Sweden.
Henry N GinsbergDepartment of Medicine, Columbia University College of Physicians and Surgeons, New York, USA.
M John ChapmanNational Institute for Health and Medical Research (INSERM), and University of Pierre and Marie Curie-Paris 6, Pitié Salpêtrière, Paris, France.
European Atherosclerosis Society Consensus Panel
Amsterdam UMC Location University of Amsterdam · NLInserm · FRUniversity of Milan · ITColumbia University · USDeutsches Diabetes-Zentrum e.V. · DEEmory University · USEuropean Atherosclerosis Society · SEGhent University Hospital · BEHacettepe University · TRHartford Hospital · USImperial College London · GBJacobs (United States) · USLouisville Metabolic and Atherosclerosis Research Center · USMedical University of Graz · ATSahlgrenska University Hospital · SESt. Michael's Hospital · CAUniversidade de São Paulo · BRUniversity of Copenhagen · DKUniversity of the Witwatersrand · ZAWestern University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aims: To objectively appraise evidence for possible adverse effects of long-term statin therapy on glucose homeostasis, cognitive, renal and hepatic function, and risk for haemorrhagic stroke or cataract. Methods and results: A literature search covering 2000-2017 was performed. The Panel critically appraised the data and agreed by consensus on the categorization of reported adverse effects. Randomized controlled trials (RCTs) and genetic studies show that statin therapy is associated with a modest increase in the risk of new-onset diabetes mellitus (about one per thousand patient-years), generally defined by laboratory findings (glycated haemoglobin ≥6.5); this risk is significantly higher in the metabolic syndrome or prediabetes. Statin treatment does not adversely affect cognitive function, even at very low levels of low-density lipoprotein cholesterol and is not associated with clinically significant deterioration of renal function, or development of cataract. Transient increases in liver enzymes occur in 0.5-2% of patients taking statins but are not clinically relevant; idiosyncratic liver injury due to statins is very rare and causality difficult to prove. The evidence base does not support an increased risk of haemorrhagic stroke in individuals without cerebrovascular disease; a small increase in risk was suggested by the Stroke Prevention by Aggressive Reduction of Cholesterol Levels study in subjects with prior stroke but has not been confirmed in the substantive evidence base of RCTs, cohort studies and case-control studies. Conclusion: Long-term statin treatment is remarkably safe with a low risk of clinically relevant adverse effects as defined above; statin-associated muscle symptoms were discussed in a previous Consensus Statement. Importantly, the established cardiovascular benefits of statin therapy far outweigh the risk of adverse effects.

Indexed as

CataractCerebral HemorrhageChemical and Drug Induced Liver InjuryCognition DisordersGlucoseHomeostasisHumansHydroxymethylglutaryl-CoA Reductase InhibitorsKidney DiseasesStrokeGlucoseHydroxymethylglutaryl-CoA Reductase Inhibitors

Identifiers

PMID29718253
PMCPMC6047411
OpenAlexW2801534920

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.