No association was found between statin intake and the risk of non-cardiovascular disease (non-CVD) outcomes or adverse effects in patients using statins to reduce cardiac-related morbidity and mortality, according to a study published in the Annals of Internal Medicine.

Investigators of this umbrella review sought to evaluate the validity and credibility of the evidence regarding associations between statin use and non-CVD outcomes, as well as associated adverse effects of statin intake.

Performing a systematic search of MEDLINE and EMBASE databases, the investigators extracted data from meta-analyses of 112 observational studies and 144 randomized controlled trials that reported non-CVD outcomes from statin use. From these meta-analyses, 278 unique non-CVD outcomes were explored for evidence of an association with statin intake. To classify the evidence, 4 categories were devised based on summary effects and 95% confidence intervals: convincing (class I), highly suggestive (class II), suggestive (class III), and weak (class IV). Credibility was further assessed on the basis of previous criteria, which considered the amount of evidence, the statistical significance of evidence, between-study heterogeneity, and small-study effect.

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The researchers found no convincing evidence for the observational studies. However, they did find 2 highly suggestive associations, 21 suggestive associations, and 42 weak associations. The class II associations included evidence of reduced cancer-related mortality in patients with cancer and diminished exacerbation in patients with chronic obstructive pulmonary disease. The only outcome from the randomized controlled trials to achieve sufficient evidence of associated statin use was decreased all-cause mortality in patients with chronic kidney disease. For associated adverse events, suggestive evidence that statins increased the risk for diabetes and myopathy was reported only among observational studies; however, no significant adverse effects were found among the randomized controlled trials.

Limitations of this review included focusing only on existing meta-analyses, thereby excluding outcomes with no meta-analysis, as well as the inability to appraise the quality of the studies. The studies lacked data on secondary outcomes and could not be assessed for credibility. Finally, the thresholds of credibility were adopted from previously established metrics, which were often arbitrary and should not be considered absolute.

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The researchers concluded that current clinical recommendations regarding the role of statins for managing cardiovascular disease should be left unchanged, writing, “The absence of harmful effects, especially those with highly convincing or highly suggestive evidence, is reassuring.”

Disclosures: Dr Campbell reports a Cancer Research UK grant outside of the submitted work. No other authors declare conflicts.


He Y, Li X, Gasevic D, et al. Statins and multiple noncardiovascular outcomes: umbrella review of meta-analyses of observational studies and randomized controlled trials [published online October 9, 2018]. Ann Intern Med. doi:10.7326/M18-0808