Clinical Question

Does lipid lowering reduce major vascular events in patients 75 years and older?

Bottom Line

This meta-analysis inappropriately conflates studies of primary and secondary prevention, and the authors argue that their data support the use of lipid-lowering drugs in older adults. That may be true for secondary prevention, but it is clearly not proven for primary prevention. The STAREE trial is currently recruiting 18,000 older adults and randomizing them to receive atorvastatin (Lipitor), 40 mg, or placebo, and it will hopefully provide greater clarity about the use of lipids for primary prevention (results expected in 2023). (Level of Evidence = 1a−)

Synopsis

Previous studies have found attenuation of the benefit of statins in older patients, especially in those older than 75 years. This meta-analysis included 24 of 28 studies from an individual patient data meta-analysis of statin trials (excluding four studies that were limited to patients with heart failure or who were on dialysis), as well as a newly published statin trial, two ezetimibe (Zetia) trials, and two proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor trials. The authors treat the individual patient data meta-analysis as a single large study: it provided 11,108 of the 21,492 patients 75 years and older in this meta-analysis. The other studies ranged in size from 642 to 3,411 patients. It is important to note that many of the studies in the individual patient data meta-analysis and four of the five other studies were of secondary prevention rather than primary prevention. For the statin trials, the relative risk of major vascular events (i.e., cardiovascular death, myocardial infarction, acute coronary syndrome, coronary revascularization, or stroke) was 0.82 (95% CI, 0.73 to 0.91). For the four nonstatin trials, the relative risk was 0.67, but with a broader confidence interval (95% CI, 0.47 to 0.95). The authors then provided a combined estimate for statin and nonstatin trials, mixing primary and secondary prevention. For primary prevention using statins there was no significant reduction in major vascular events, with 2.6% per year in the statin group and 2.7% in the control group. There was no difference in all-cause mortality for primary or secondary prevention studies of statins or nonstatins (relative risk = 0.97; 95% CI, 0.82 to 1.15).

Study design: Systematic review

Funding source: Unknown/not stated

Setting: Outpatient (any)

Reference: Gencer B, Marston N, AIm K, et al. Efficacy and safety of lowering LDL cholesterol in older patients: a systematic review and meta-analysis of randomised controlled trials. Lancet. 2020;396(10263):1637–1643.

Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.