High tierMeta Analysis Of RctsCitation verified
The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials
Cholesterol Treatment Trialists' (CTT) Collaborators, B Mihaylova, J Emberson, C Baigent - The Lancet, 2012
In an individual-participant meta-analysis of 27 statin trials, each 1.0 mmol/L LDL reduction cut major vascular events by about 21%, and the proportional benefit was at least as large in the lowest-risk people. In those with 5-year risk under 10%, that translated to about 11 fewer major vascular events per 1,000 over 5 years.
Key findings
- Major vascular events: RR 0.79 (95% CI 0.77-0.81) per 1.0 mmol/L LDL reduction, largely regardless of baseline risk.
- Proportional benefit at least as large in the two lowest baseline-risk groups.
- In people with <10% 5-year risk, ~11 fewer major vascular events per 1,000 over 5 years per 1 mmol/L reduction.
- All-cause mortality reduced in those without prior vascular disease (RR 0.91, 95% CI 0.85-0.97); no excess cancer.
Effect measures
- Relative Risk Reduction: 21% fewer major vascular events per 1.0 mmol/L LDL-C reduction (RR 0.79)95% CI 0.77-0.81
- Absolute Risk Reduction: ~11 fewer major vascular events per 1,000 people over 5 yearsBaseline risk: 5-year major-vascular-event risk below 10%
Why this evidence tier (High)
- Risk of bias:
- Individual-participant meta-analysis of randomized trials - the strongest design for treatment benefit; conducted by an established collaboration.
- Precision:
- Very large (174k) with many events; precise estimates.
- Directness:
- Directly measures hard clinical events from LDL lowering.
- Consistency:
- Consistent proportional benefit across risk strata.
- Funding / COI:
- Funded by public/charitable bodies (BHF, MRC, Cancer Research UK, NHMRC); the CTT holds trial data including industry-sponsored trials.
High certainty for the relative benefit; note the absolute benefit in low-risk primary prevention is modest and is the locus of debate.
- Population:
- 174,149 participants across 27 randomised trials, stratified by baseline 5-year major-vascular-event risk; emphasis on low-risk individuals.
- Conflicts of interest:
- Underlying trials include industry-sponsored studies; the CTT collaboration is academically led. See source for full disclosures.
- Funding:
- British Heart Foundation; UK Medical Research Council; Cancer Research UK; European Community Biomed Programme; Australian NHMRC; National Heart Foundation (Australia).
Limitations
- Per-protocol meta-analysis of trial data; adverse effects not the focus of this report.
- Absolute benefit in low-risk primary prevention is small and value-dependent.