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

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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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Additional file 4 of Optimal target of LDL cholesterol level for statin treatment: challenges to monotonic relationship with cardiovascular events
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Additional file 3 of Optimal target of LDL cholesterol level for statin treatment: challenges to monotonic relationship with cardiovascular events
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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: Byrne, Paula
Demasi, Maryanne
Jones, Mark
Smith, Susan M.
O’Brien, Kirsty K.
DuBroff, Robert
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: green
www.ncbi.nlm.nih.gov
Locations: JAMA Internal Medicine (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Bond University Research Portal (Bond University) (submittedVersion, other-oa)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › 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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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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