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Meta-Analysis
. 2022 May 1;182(5):474-481.
doi: 10.1001/jamainternmed.2022.0134.

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

Paula Byrne  1 , Maryanne Demasi  2 , Mark Jones  3 , Susan M Smith  1   4 , Kirsty K O'Brien  5 , Robert DuBroff  6
Affiliations
Meta-Analysis

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

Paula Byrne et al. JAMA Intern Med. .

Erratum in

  • Error in Figure 3.
    [No authors listed] [No authors listed] JAMA Intern Med. 2022 May 1;182(5):579. doi: 10.1001/jamainternmed.2022.1671. JAMA Intern Med. 2022. PMID: 35499770 Free PMC article. No abstract available.

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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Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.
Figure 1.. Comparison of Absolute and Relative Risk Reductions of Statins, All Trials
Figure 2.
Figure 2.. Association Between Relative Risk Reductions in All-Cause Mortality, Myocardial Infarction (MI), and Stroke and Between-Group Difference in Achieved Low-Density Lipoprotein Cholesterol (LDL-C) Level
Figure 3.
Figure 3.. Association Between Absolute Risk Reductions in All-Cause Mortality, Myocardial Infarction (MI), and Stroke and Between-Group Difference in Achieved Low-Density Lipoprotein Cholesterol (LDL-C) Level
See this image and copyright information in PMC

Comment in

References

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