Yazhou He, MD; Xue Li, MSc; Danijela Gasevic, MD, PhD; Eleanor Brunt, BMedSci; Fiona McLachlan, BSc, MBChB; Marisa Millenson, MSc; Maria Timofeeva, PhD; John P.A. Ioannidis, MD, DSc; Harry Campbell, MD; Evropi Theodoratou, MSc, PhD
Grant Support: Dr. He and Ms. Li are supported by the China Scholarship Council. Dr. Theodoratou is supported by a Cancer Research UK (CRUK) Career Development Fellowship (C31250/A22804).
Disclosures: Dr. Campbell reports a CRUK grant outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-0808.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol: Available from Dr. Theodoratou (e-mail, E.Theodoratou@ed.ac.uk). Statistical code: See Methods and Appendix. Data set: See Supplement Tables 1 to 6.
Corresponding Author: Evropi Theodoratou, MSc, PhD, Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, United Kingdom; e-mail, E.Theodoratou@ed.ac.uk.
Current Author Addresses: Drs. He and Theodoratou, Ms. Li, and Prof. Campbell: Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, United Kingdom.
Dr. Gasevic: School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne VIC 3004, Victoria, Australia.
Ms. Brunt and Dr. McLachlan: The University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG, United Kingdom.
Ms. Millenson: Children's Hospital of Philadelphia, Center for Pediatric Clinical Effectiveness, 2716 South Street, Philadelphia, PA 19146.
Dr. Timofeeva: Colon Cancer Genetics Group, 4th Floor MRC-HGU, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, United Kingdom.
Prof. Ioannidis: Stanford Prevention Research Center, Stanford University School of Medicine, Medical School Office Building, 1265 Welch Road, Mail Code 5411, Stanford, CA 94305.
Author Contributions: Conception and design: X. Li, D. Gasevic, J.P.A. Ioannidis, H. Campbell, E. Theodoratou.
Analysis and interpretation of the data: Y. He, X. Li, J.P.A. Ioannidis, H. Campbell.
Drafting of the article: Y. He, D. Gasevic, E. Brunt, J.P.A. Ioannidis, E. Theodoratou.
Critical revision for important intellectual content: Y. He, X. Li, D. Gasevic, M. Timofeeva, J.P.A. Ioannidis, H. Campbell, E. Theodoratou.
Final approval of the article: Y. He, X. Li, D. Gasevic, E. Brunt, F. McLachlan, M. Millenson, M. Timofeeva, J.P.A. Ioannidis, H. Campbell, E. Theodoratou.
Statistical expertise: X. Li, J.P.A. Ioannidis, E. Theodoratou.
Administrative, technical, or logistic support: X. Li, M. Millenson, H. Campbell.
Collection and assembly of data: Y. He, X. Li, D. Gasevic, F. McLachlan, M. Millenson, J.P.A. Ioannidis.
Many effects of statins on non–cardiovascular disease (non-CVD) outcomes have been reported.
To evaluate the quantity, validity, and credibility of evidence regarding associations between statins and non-CVD outcomes and the effects of statins on these outcomes.
MEDLINE and EMBASE (English terms only, inception to 28 May 2018).
Meta-analyses (published in English) of observational studies and of randomized controlled trials (RCTs) that examined non-CVD outcomes of statin intake.
Two investigators extracted data from meta-analyses and individual studies. Credibility assessments based on summary effect sizes from a random-effects model, between-study heterogeneity, 95% prediction interval, small-study effect, excess significance, and credibility ceilings were devised to classify evidence.
This review explored 278 unique non-CVD outcomes from 112 meta-analyses of observational studies and 144 meta-analyses of RCTs. For observational studies, no convincing (class I) evidence, 2 highly suggestive (class II) associations (decreased cancer mortality in patients with cancer and decreased exacerbation in patients with chronic obstructive pulmonary disease), 21 suggestive (class III) associations, and 42 weak (class IV) associations were identified. One outcome from the RCTs (decreased all-cause mortality in patients with chronic kidney disease) attained a sufficient amount of evidence with no hints of bias. For adverse events, observational studies showed suggestive evidence that statins increase the risk for diabetes and myopathy. Among the RCTs, no statistically significant effects were found on myopathy, myalgia, or rhabdomyolysis.
Studies with relevant data and outcomes not included in the meta-analyses may have been missed. Credibility assessments relied on several assumptions and arbitrary thresholds.
The absence of convincing evidence of an association between statins and non-CVD outcomes supports leaving the current recommendations unchanged.
He Y, Li X, Gasevic D, Brunt E, McLachlan F, Millenson M, et al. Statins and Multiple Noncardiovascular Outcomes: Umbrella Review of Meta-analyses of Observational Studies and Randomized Controlled Trials. Ann Intern Med. [Epub ahead of print 9 October 2018]169:543–553. doi: 10.7326/M18-0808
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Published: Ann Intern Med. 2018;169(8):543-553.
Published at www.annals.org on 9 October 2018
Cardiology, Coronary Risk Factors, Dyslipidemia.
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