Statins and multiple noncardiovascular outcomes

Umbrella review of meta-Analyses of observational studies and randomized controlled trials

Yazhou He, Xue Li, Danijela Gasevic, Eleanor Brunt, Fiona McLachlan, Marisa Millenson, Maria Timofeeva, John P.A. Ioannidis, Harry Campbell, Evropi Theodoratou

Research output: Contribution to journalReview ArticleResearchpeer-review

10 Citations (Scopus)

Abstract

Background: Many effects of statins on non-cardiovascular disease (non-CVD) outcomes have been reported. Purpose: 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. Data Sources: MEDLINE and EMBASE (English terms only, inception to 28 May 2018). Study Selection: Meta-Analyses (published in English) of observational studies and of randomized controlled trials (RCTs) that examined non-CVD outcomes of statin intake. Data Extraction: Two investigators extracted data from metaanalyses and individual studies. Credibility assessments based on summary effect sizes from a random-effects model, betweenstudy heterogeneity, 95% prediction interval, small-study effect, excess significance, and credibility ceilings were devised to classify evidence. Data Synthesis: 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. Limitations: 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. Conclusion: The absence of convincing evidence of an association between statins and non-CVD outcomes supports leaving the current recommendations unchanged. Primary Funding Source: None.

Original languageEnglish
Pages (from-to)543-553
Number of pages11
JournalAnnals of Internal Medicine
Volume169
Issue number8
DOIs
Publication statusPublished - 16 Oct 2018

Cite this

He, Yazhou ; Li, Xue ; Gasevic, Danijela ; Brunt, Eleanor ; McLachlan, Fiona ; Millenson, Marisa ; Timofeeva, Maria ; Ioannidis, John P.A. ; Campbell, Harry ; Theodoratou, Evropi. / Statins and multiple noncardiovascular outcomes : Umbrella review of meta-Analyses of observational studies and randomized controlled trials. In: Annals of Internal Medicine. 2018 ; Vol. 169, No. 8. pp. 543-553.
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title = "Statins and multiple noncardiovascular outcomes: Umbrella review of meta-Analyses of observational studies and randomized controlled trials",
abstract = "Background: Many effects of statins on non-cardiovascular disease (non-CVD) outcomes have been reported. Purpose: 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. Data Sources: MEDLINE and EMBASE (English terms only, inception to 28 May 2018). Study Selection: Meta-Analyses (published in English) of observational studies and of randomized controlled trials (RCTs) that examined non-CVD outcomes of statin intake. Data Extraction: Two investigators extracted data from metaanalyses and individual studies. Credibility assessments based on summary effect sizes from a random-effects model, betweenstudy heterogeneity, 95{\%} prediction interval, small-study effect, excess significance, and credibility ceilings were devised to classify evidence. Data Synthesis: 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. Limitations: 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. Conclusion: The absence of convincing evidence of an association between statins and non-CVD outcomes supports leaving the current recommendations unchanged. Primary Funding Source: None.",
author = "Yazhou He and Xue Li and Danijela Gasevic and Eleanor Brunt and Fiona McLachlan and Marisa Millenson and Maria Timofeeva and Ioannidis, {John P.A.} and Harry Campbell and Evropi Theodoratou",
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He, Y, Li, X, Gasevic, D, Brunt, E, McLachlan, F, Millenson, M, Timofeeva, M, Ioannidis, JPA, Campbell, H & Theodoratou, E 2018, 'Statins and multiple noncardiovascular outcomes: Umbrella review of meta-Analyses of observational studies and randomized controlled trials', Annals of Internal Medicine, vol. 169, no. 8, pp. 543-553. https://doi.org/10.7326/M18-0808

Statins and multiple noncardiovascular outcomes : Umbrella review of meta-Analyses of observational studies and randomized controlled trials. / He, Yazhou; Li, Xue; Gasevic, Danijela; Brunt, Eleanor; McLachlan, Fiona; Millenson, Marisa; Timofeeva, Maria; Ioannidis, John P.A.; Campbell, Harry; Theodoratou, Evropi.

In: Annals of Internal Medicine, Vol. 169, No. 8, 16.10.2018, p. 543-553.

Research output: Contribution to journalReview ArticleResearchpeer-review

TY - JOUR

T1 - Statins and multiple noncardiovascular outcomes

T2 - Umbrella review of meta-Analyses of observational studies and randomized controlled trials

AU - He, Yazhou

AU - Li, Xue

AU - Gasevic, Danijela

AU - Brunt, Eleanor

AU - McLachlan, Fiona

AU - Millenson, Marisa

AU - Timofeeva, Maria

AU - Ioannidis, John P.A.

AU - Campbell, Harry

AU - Theodoratou, Evropi

PY - 2018/10/16

Y1 - 2018/10/16

N2 - Background: Many effects of statins on non-cardiovascular disease (non-CVD) outcomes have been reported. Purpose: 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. Data Sources: MEDLINE and EMBASE (English terms only, inception to 28 May 2018). Study Selection: Meta-Analyses (published in English) of observational studies and of randomized controlled trials (RCTs) that examined non-CVD outcomes of statin intake. Data Extraction: Two investigators extracted data from metaanalyses and individual studies. Credibility assessments based on summary effect sizes from a random-effects model, betweenstudy heterogeneity, 95% prediction interval, small-study effect, excess significance, and credibility ceilings were devised to classify evidence. Data Synthesis: 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. Limitations: 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. Conclusion: The absence of convincing evidence of an association between statins and non-CVD outcomes supports leaving the current recommendations unchanged. Primary Funding Source: None.

AB - Background: Many effects of statins on non-cardiovascular disease (non-CVD) outcomes have been reported. Purpose: 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. Data Sources: MEDLINE and EMBASE (English terms only, inception to 28 May 2018). Study Selection: Meta-Analyses (published in English) of observational studies and of randomized controlled trials (RCTs) that examined non-CVD outcomes of statin intake. Data Extraction: Two investigators extracted data from metaanalyses and individual studies. Credibility assessments based on summary effect sizes from a random-effects model, betweenstudy heterogeneity, 95% prediction interval, small-study effect, excess significance, and credibility ceilings were devised to classify evidence. Data Synthesis: 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. Limitations: 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. Conclusion: The absence of convincing evidence of an association between statins and non-CVD outcomes supports leaving the current recommendations unchanged. Primary Funding Source: None.

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U2 - 10.7326/M18-0808

DO - 10.7326/M18-0808

M3 - Review Article

VL - 169

SP - 543

EP - 553

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

SN - 0003-4819

IS - 8

ER -