The DOI matches its Crossref record; 51 of the 54 references it cites were found in a registry or an index.
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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Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & The PRISMA Group (2009) · PLoS Medicine · doi:10.1371/journal.pmed.1000097 · Cited by 64,042
RoB 2: a revised tool for assessing risk of bias in randomised trials
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Self-citation
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Cited by
Sorted by citations
2024 ESC Guidelines for the management of chronic coronary syndromes
Vrints, C. J., Andreotti, F., Koskinas, K. C., Rosselló, X., Adamo, M., Ainslie, J., BANNING, A. P., Budaj, A., Buechel, R. R., Chiariello, G. A., et al. (2024) · European Heart Journal · doi:10.1093/eurheartj/ehae177 · Cited by 3,521
Ridker, P. M., Bhatt, D. L., Pradhan, A. D., Glynn, R. J., MacFadyen, J. G., & Nissen, S. E. (2023) · The Lancet · doi:10.1016/s0140-6736(23)00215-5 · Cited by 724
2023 Chinese guideline for lipid management
Li, J., Zhao, S., Zhao, D. H., Lü, G., Peng, D., Liu, J., Chen, Z., Guo, Y., Wu, N., Yan, S.-K., et al. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1190934 · Cited by 241
Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients
Nissen, S. E., Menon, V., Nicholls, S. J., Brennan, D., Laffin, L., Ridker, P., Ray, K. K., Mason, D., Kastelein, J. J. P., Cho, L., et al. (2023) · JAMA · doi:10.1001/jama.2023.9696 · Cited by 146
2023 China Guidelines for Lipid Management
Li, J., Zhao, S., Zhao, D., Lü, G., Peng, D., Liu, J., Chen, Z., Guo, Y., Wu, N., Yan, S.-K., et al. (2023) · 老年心脏病学杂志：英文版 · doi:10.26599/1671-5411.2023.09.008 · Cited by 120
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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