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.
UR - http://www.scopus.com/inward/record.url?scp=85055079791&partnerID=8YFLogxK
U2 - 10.7326/M18-0808
DO - 10.7326/M18-0808
M3 - Review Article
C2 - 30304368
AN - SCOPUS:85055079791
SN - 0003-4819
VL - 169
SP - 543
EP - 553
JO - Annals of Internal Medicine
JF - Annals of Internal Medicine
IS - 8
ER -