Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment: A Systematic Review and Meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized clinical trials
PubMed 35285850 · doi:10.1001/jamainternmed.2022.0134
What was done
Search of PubMed and Embase (January 1987 to June 2021) for large randomized clinical trials comparing statins to placebo or usual care in adults with at least 2 years of planned follow-up and reported absolute LDL-C changes. Three reviewers assessed study quality using the Risk of Bias 2 tool and certainty using GRADE. Meta-analyses and meta-regression evaluated absolute and relative risk reductions for all-cause mortality, myocardial infarction, and stroke.
What was found
In 21 trials, statins reduced absolute risk by 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. Associated relative risk reductions were 9% (95% CI, 5%-14%), 29% (95% CI, 22%-34%), and 14% (95% CI, 5%-22%), respectively. Meta-regression evaluating the mediating association of the magnitude of LDL-C lowering with outcomes was inconclusive.
Why it matters
Statin therapy yields modest absolute risk reductions for individual mortality and vascular outcomes despite substantially larger relative risk reductions. Presenting absolute risk changes is critical for informed shared decision-making in clinical practice.
Limits
Meta-regression could not establish a conclusive relationship between the degree of LDL-C reduction and individual clinical outcomes. Evidence certainty was downgraded due to significant heterogeneity across included studies. Total participant count was not reported in the abstract.
Cited by
- supports A systematic review of over 30 randomized controlled trials found no clear relationship between the degree of LDL reduction from cholesterol-lowering drugs and prevention of cardiovascular events.