Extent of Low-density Lipoprotein Cholesterol Reduction and All-cause and Cardiovascular Mortality Benefit: A Systematic Review and Meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 36027598 · doi:10.1097/FJC.0000000000001345
What was done
Authors searched PubMed and ClinicalTrials.gov from inception to December 31, 2019, for randomized controlled trials comparing lipid-modifying agents (statins, ezetimibe, PCSK-9 inhibitors) versus placebo, usual care, or less-intensive LDL-C-lowering therapy in adults with or without cardiovascular disease, with at least 52 weeks of follow-up. Primary endpoints were all-cause and cardiovascular mortality; secondary endpoints were myocardial infarction, stroke, and non-cardiovascular death. Absolute risk differences (ARDs per 1000 person-years), number needed to treat (NNT), and rate ratios (RR) were calculated across 60 trials totaling 323,950 participants.
What was found
Active or more potent lipid-lowering therapy reduced all-cause mortality compared with control: ARD -1.33 (95% CI -1.89 to -0.76) per 1000 person-years; NNT 754 (95% CI 529 to 1309); RR 0.92 (95% CI 0.89 to 0.96). However, intensive LDL-C percent lowering was not associated with further reductions in all-cause mortality [ARD -0.27 (95% CI -1.24 to 0.71); RR 1.00 (95% CI 0.94 to 1.06)] or cardiovascular mortality [ARD -0.28 (95% CI -0.83 to 0.38); RR 1.02 (95% CI 0.94 to 1.09)]. Numerical results for secondary endpoints (myocardial infarction, stroke, non-CV death) were not reported in the abstract.
Why it matters
This meta-analysis demonstrates that while initiating lipid-lowering therapy confers an overall survival benefit, achieving greater percentage reductions in LDL-C yields no incremental reduction in all-cause or cardiovascular mortality across broad populations.
Limits
The abstract reports no numerical findings for non-fatal secondary cardiovascular outcomes or subgroup analyses. Trial-level meta-regression cannot substitute for individual patient data to identify specific subgroups that might benefit from intensive lowering. Follow-up of 52 weeks or longer varied across included studies.
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