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Cited by 114Lipoproteins and Cardiovascular HealthCancer, Lipids, and MetabolismAcute Myocardial Infarction Research

Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment: A Systematic Review and Meta-analysis

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Byrne, Paula, Demasi, Maryanne, Jones, Mark, Smith, Susan M., O’Brien, Kirsty K., DuBroff, Robert·2022·JAMA Internal Medicine
DOI 10.1001/jamainternmed.2022.0134PMC PMC8922205
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Abstract

Importance: The association between statin-induced reduction in low-density lipoprotein cholesterol (LDL-C) levels and the absolute risk reduction of individual, rather than composite, outcomes, such as all-cause mortality, myocardial infarction, or stroke, is unclear. Objective: To assess the association between absolute reductions in LDL-C levels with treatment with statin therapy and all-cause mortality, myocardial infarction, and stroke to facilitate shared decision-making between clinicians and patients and inform clinical guidelines and policy. Data Sources: PubMed and Embase were searched to identify eligible trials from January 1987 to June 2021. Study Selection: Large randomized clinical trials that examined the effectiveness of statins in reducing total mortality and cardiovascular outcomes with a planned duration of 2 or more years and that reported absolute changes in LDL-C levels. Interventions were treatment with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) vs placebo or usual care. Participants were men and women older than 18 years. Data Extraction and Synthesis: Three independent reviewers extracted data and/or assessed the methodological quality and certainty of the evidence using the risk of bias 2 tool and Grading of Recommendations, Assessment, Development and Evaluation. Any differences in opinion were resolved by consensus. Meta-analyses and a meta-regression were undertaken. Main Outcomes and Measures: Primary outcome: all-cause mortality. Secondary outcomes: myocardial infarction, stroke. Findings: Twenty-one trials were included in the analysis. Meta-analyses showed reductions in the absolute risk of 0.8% (95% CI, 0.4%-1.2%) for all-cause mortality, 1.3% (95% CI, 0.9%-1.7%) for myocardial infarction, and 0.4% (95% CI, 0.2%-0.6%) for stroke in those randomized to treatment with statins, with associated relative risk reductions of 9% (95% CI, 5%-14%), 29% (95% CI, 22%-34%), and 14% (95% CI, 5%-22%) respectively. A meta-regression exploring the potential mediating association of the magnitude of statin-induced LDL-C reduction with outcomes was inconclusive. Conclusions and Relevance: The results of this meta-analysis suggest that the absolute risk reductions of treatment with statins in terms of all-cause mortality, myocardial infarction, and stroke are modest compared with the relative risk reductions, and the presence of significant heterogeneity reduces the certainty of the evidence. A conclusive association between absolute reductions in LDL-C levels and individual clinical outcomes was not established, and these findings underscore the importance of discussing absolute risk reductions when making informed clinical decisions with individual patients.

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Crossref · 10.1001/jamainternmed.2022.0134

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  • Recent data are limited on the effects of statins or other adjunctive treatments in patients without a history of a cardiovascular event.

    “Recent data are limited on the effects of statins or other adjunctive treatments in patients without a history of a cardiovascular event, leading some authors to question whether the benefits of cholesterol lowering exceed the harms in these patients.[4][5][6][7]”

    From Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients (2023) · cites this paper as [7]

    The Abstract and Conclusions say the absolute benefits of statins are modest and that heterogeneity limits certainty. The Results also report effects for primary-prevention patients, so the paper does not establish that data on statin effects in this group are generally limited. It does not assess other adjunctive treatments. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • The effects of bempedoic acid on cardiovascular outcomes in statin-intolerant patients without a prior cardiovascular event (primary prevention) have not been fully described.

    “The effects of bempedoic acid on cardiovascular outcomes in statin-intolerant patients without a prior cardiovascular event (primary prevention) have not been fully described.”

    From Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients (2023) · cites this paper as [7]

    The Abstract and Methods describe a review of statin trials, including primary-prevention trials, but do not address bempedoic acid or statin-intolerant patients. Searches for “bempedoic acid” and the claimed primary-prevention population found no passage assessing whether bempedoic acid’s cardiovascular effects had been fully described. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

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3 of the 54 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. [11]Vine DL, Hastings GE. Ischaemic heart disease and cholesterol: absolute risk more informative than relative risk. BMJ. 1994;308:1040-1041. [PMC free article] [PubMed] [Google Scholar]
  2. [15]Covidence. Better systematic review management. Accessed October 27, 2020. http://www.covidence.org

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Authors
Byrne, P., Demasi, M., Jones, M., Smith, S. M., O’Brien, K. K., & DuBroff, R.
Affiliations
  • Royal College of Surgeons in Ireland (IE)
  • Institute for Scientific Freedom, Copenhagen, Denmark
  • Bond University (AU)
  • Independent researcher, Dublin, Ireland
  • University of New Mexico (US)
Corresponding author
Byrne, Paula
ORCID
Venue
JAMA Internal Medicine
Publisher
American Medical Association (AMA)
Published
2022-05-01
Volume
182
Issue
5
Pages
474
ISSN
2168-6106 (ISSN-L)
DOI
10.1001/jamainternmed.2022.0134
PMC
PMC8922205
OpenAlex
W4220974542
Cited by
114
References
54
Citations by year
2026: 19 · 2025: 24 · 2024: 28 · 2023: 26 · 2022: 17
FWCI
5.64
Type
journal article
Language
en
Open access
Locations
  • JAMA Internal Medicine (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Bond University Research Portal (Bond University) (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
Keywords
statins, LDL cholesterol lowering, all-cause mortality, myocardial infarction, stroke, absolute risk reduction, relative risk reduction, cardiovascular outcomes, shared decision-making, cardiovascular risk prediction models
MeSH terms
Cardiovascular Diseases, Female, Humans, Cholesterol, LDL, Male, Myocardial Infarction, Randomized Controlled Trials as Topic, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Stroke

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