High tierMeta Analysis Of RctsCitation verified
Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials
Cholesterol Treatment Trialists' (CTT) Collaboration, C Baigent, L Blackwell, J Emberson, R Collins - The Lancet, 2010
A large meta-analysis of 26 statin trials found dose-dependent reductions in cardiovascular events with LDL lowering: each 1.0 mmol/L reduction cut major vascular events by about 22%, with no threshold below which benefit ceased, and a roughly 10% reduction in all-cause mortality per 1.0 mmol/L.
Key findings
- Major vascular events: rate ratio 0.78 (95% CI 0.76-0.80) per 1.0 mmol/L LDL-C reduction.
- More intensive vs less intensive statin therapy: further 15% reduction (95% CI 11-18).
- All-cause mortality reduced ~10% per 1.0 mmol/L LDL-C reduction; no threshold observed; no excess cancer.
Effect measures
- Relative Risk Reduction: 22% fewer major vascular events per 1.0 mmol/L LDL-C reduction (RR 0.78)95% CI 0.76-0.80
- Relative Risk Reduction: ~10% lower all-cause mortality per 1.0 mmol/L LDL-C reduction
Why this evidence tier (High)
- Risk of bias:
- Individual-participant meta-analysis of randomized trials by an established collaboration.
- Precision:
- Very large (169k) with many events; high precision; no threshold detected.
- Directness:
- Directly measures hard clinical events and mortality from LDL lowering.
- Consistency:
- Dose-dependent, consistent across trials.
- Funding / COI:
- Public/charitable funding (MRC, BHF, etc.); underlying trials include industry-sponsored studies.
High certainty that lowering LDL reduces events dose-dependently - strong supporting evidence for causality via intervention.
- Population:
- About 169,138 participants across 26 randomised statin trials (5 more-vs-less-intensive, 21 statin-vs-control), primary and secondary prevention.
- Conflicts of interest:
- Underlying trials include industry-sponsored studies; collaboration is academically led. See source.
- Funding:
- UK Medical Research Council; British Heart Foundation; European Community Biomed Programme; Australian NHMRC; National Heart Foundation.
Limitations
- Treatment effect (drug) does not isolate LDL from statins' other effects, though concordance with non-statin LDL lowering supports the LDL interpretation.
- Mixed primary/secondary prevention; this report emphasises efficacy/safety overall.