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Cited by 318Lipoproteins and Cardiovascular HealthAntiplatelet Therapy and Cardiovascular DiseasesCoronary Interventions and Diagnostics

Efficacy and safety of lowering LDL cholesterol in older patients: a systematic review and meta-analysis of randomised controlled trials

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Gencer, Baris, Marston, Nicholas A, Im, KyungAh, Cannon, Christopher P, Sever, Peter, Keech, Anthony, Braunwald, Eugene, Giugliano, Robert P +1 more·2020·The Lancet
DOI 10.1016/s0140-6736(20)32332-1PMC PMC8015314
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Abstract

Background The clinical benefit of LDL cholesterol lowering treatment in older patients remains debated. We aimed to summarise the evidence of LDL cholesterol lowering therapies in older patients. Methods In this systematic review and meta-analysis, we searched MEDLINE and Embase for articles published between March 1, 2015, and Aug 14, 2020, without any language restrictions. We included randomised controlled trials of cardiovascular outcomes of an LDL cholesterol-lowering drug recommended by the 2018 American College of Cardiology and American Heart Association guidelines, with a median follow-up of at least 2 years and data on older patients (aged ≥75 years). We excluded trials that exclusively enrolled participants with heart failure or on dialysis because guidelines do not recommend lipid-lowering therapy in such patients who do not have another indication. We extracted data for older patients using a standardised data form for aggregated study-level data. We meta-analysed the risk ratio (RR) for major vascular events (a composite of cardiovascular death, myocardial infarction or other acute coronary syndrome, stroke, or coronary revascularisation) per 1 mmol/L reduction in LDL cholesterol. Findings Data from six articles were included in the systematic review and meta-analysis, which included 24 trials from the Cholesterol Treatment Trialists' Collaboration meta-analysis plus five individual trials. Among 244 090 patients from 29 trials, 21 492 (8·8%) were aged at least 75 years, of whom 11 750 (54·7%) were from statin trials, 6209 (28·9%) from ezetimibe trials, and 3533 (16·4%) from PCSK9 inhibitor trials. Median follow-up ranged from 2·2 years to 6·0 years. LDL cholesterol lowering significantly reduced the risk of major vascular events (n=3519) in older patients by 26% per 1 mmol/L reduction in LDL cholesterol (RR 0·74 [95% CI 0·61-0·89]; p=0·0019), with no statistically significant difference with the risk reduction in patients younger than 75 years (0·85 [0·78-0·92]; p interaction=0·37). Among older patients, RRs were not statistically different for statin (0·82 [0·73-0·91]) and non-statin treatment (0·67 [0·47-0·95]; p interaction=0·64). The benefit of LDL cholesterol lowering in older patients was observed for each component of the composite, including cardiovascular death (0·85 [0·74-0·98]), myocardial infarction (0·80 [0·71-0·90]), stroke (0·73 [0·61-0·87]), and coronary revascularisation (0·80 [0·66-0·96]). Interpretation In patients aged 75 years and older, lipid lowering was as effective in reducing cardiovascular events as it was in patients younger than 75 years. These results should strengthen guideline recommendations for the use of lipid-lowering therapies, including non-statin treatment, in older patients. Funding None.

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  • There is less evidence for lipid-lowering therapy and aspirin therapy, although the benefits of these interventions for primary and secondary prevention are likely to apply to older adults whose life expectancies equal or exceed the time frames of the clinical trials.

    “There is less evidence for lipid-lowering therapy and aspirin therapy, although the benefits of these interventions for primary and secondary prevention are likely to apply to older adults whose life expectancies equal or exceed the time frames of the clinical trials (74).”

    From 13. Older Adults: Standards of Care in Diabetes—2025 (2025) · cites this paper as [74]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

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  • The benefits of lipid-lowering therapy and aspirin for primary and secondary prevention are likely to apply to older adults whose life expectancies equal or exceed the time frames of the clinical trials.

    “the benefits of these interventions for primary and secondary prevention are likely to apply to older adults whose life expectancies equal or exceed the time frames of the clinical trials”

    From 13. Older Adults: Standards of Care in Diabetes—2026 (2026) · cites this paper as [82]

    The Results (page unavailable) report that LDL-lowering therapy reduced major vascular events in adults aged 75 or older, with no evidence of a treatment difference between those with and without established cardiovascular disease. The Discussion (page unavailable) notes that benefits emerge over several years, but the paper does not evaluate aspirin or establish the claim's specific life-expectancy threshold. It also cautions that primary-prevention data in older patients are sparse. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In the case of statins, the follow-up time of clinical trials ranged from 2 to 6 years.

    “In the case of statins, the follow-up time of clinical trials ranged from 2 to 6 years.”

    From 13. Older Adults: Standards of Care in Diabetes—2026 (2026) · cites this paper as [82]

    The Results report median follow-up of 2.2 to 6.0 years, approximately the claimed range. That range describes all 29 trials, including non-statin trials; the passage does not establish it as the range for statin trials alone. No page number is available in our copy. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Gencer, B., Marston, N. A., Im, K., Cannon, C. P., Sever, P., Keech, A., Braunwald, E., Giugliano, R. P., & Sabatine, M. S.
Affiliations
  • Harvard University (US)
  • Brigham and Women's Hospital (US)
  • Imperial College London (GB)
  • The University of Sydney (AU)
Corresponding author
Sabatine, Marc S
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2020-11
Volume
396
Issue
10263
Pages
1637-1643
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(20)32332-1
PMC
PMC8015314
OpenAlex
W3099601560
Cited by
318
References
5
Citations by year
2026: 24 · 2025: 58 · 2024: 65 · 2023: 58 · 2022: 54 · 2021: 54 · 2020: 4
FWCI
9.63
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • IRIS (submittedVersion)
Funders
National Heart, Lung, and Blood Institute (L30 HL143770, K08HL153950, F32HL144029)
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Coronary Interventions and Diagnostics
Keywords
LDL cholesterol lowering, elderly patients, statins, ezetimibe, PCSK9 inhibitors, major vascular events, cardiovascular outcomes, lipid-lowering therapy, age interaction, cardiovascular mortality, myocardial infarction, stroke, coronary revascularization, treatment efficacy and safety, ACC/AHA guidelines, heart failure, dialysis, frailty
MeSH terms
Ezetimibe, Aged, Anticholesteremic Agents, Cardiovascular Diseases, Humans, Cholesterol, LDL, Myocardial Infarction, Randomized Controlled Trials as Topic, Treatment Outcome, Stroke, Risk Reduction Behavior

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