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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
Open accessAbstract
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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“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]
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“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]
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Metadata
- 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
- Venue
- JAMA Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 2022-05-01
- Volume
- 182
- Issue
- 5
- Pages
- 474
- ISSN
- 2168-6106 (ISSN-L)
- 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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