Review Questions Evidence on Statins for Non-CVD Outcomes

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There is a “dearth of convincing evidence” that lipid-lowering treatment with statin drugs plays any major role in improving outcomes other than cardiovascular disease (CVD), concludes a review and meta-analysis in Annals of Internal Medicine.

The researchers report an “umbrella” review of 268 previous meta-analyses of data on non-CVD outcomes of statin treatment. Their review identified 144 papers reporting 297 meta-analyses of randomized controlled trials (RCTs) and 112 papers reporting 268 meta-analyses of observational studies. The analysis examined a total of 278 unique non-CVD outcomes. It included credibility assessments incorporating summary effect sizes, study heterogeneity, 95% prediction intervals, study size, and significance bias.

On analysis of RCT data, there was only one significant statin-related non-CVD outcome with a sufficient amount of evidence and no sign of bias: reduced all-cause mortality in patients with chronic kidney disease. Analysis of observational data found no “convincing” associations and two “suggestive” associations: decreased cancer mortality in patients with cancer and decreased exacerbation rate in patients with chronic obstructive pulmonary disease. The observational data also showed “weak” associations for 42 additional non-CVD outcomes.

Analysis of adverse events in the RCT data found no effects of statins on risks for myopathy, myalgia, or rhabdomyolysis. For the observational studies, there was “suggestive” evidence for increased risks of diabetes and myopathy.

Statins have well-demonstrated benefits in reducing the risk of heart disease and stroke. Although many studies have suggested that statins can improve various non-CVD outcomes, the evidence supporting these benefits is less clear.

Only a few of the reported effects of statins on non-CVD outcomes show convincing evidence of a credible association, according to the umbrella review of existing meta-analyses. Even the reduction in all-cause mortality in chronic kidney disease might be attributable to CVD events, the authors suggest. They conclude that their findings “do not support any change in the existing clinical recommendations regarding statin use for non-CVD conditions” [He Y, et al. Statins and multiple noncardiovascular outcomes: umbrella review of meta-analyses of observational studies and randomized controlled trials. Ann Intern Med 2018; 169:543–553].