Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.
Level 1 - systematic review of randomized trials
Prospective meta-analysis of 14 randomized controlled trials
PubMed 16214597 · doi:10.1016/S0140-6736(05)67394-1
What was done
A prospective meta-analysis evaluated individual participant data from 90,056 individuals across 14 randomized controlled trials of statins with a mean follow-up of 5 years. Weighted estimates were calculated to measure the effect on vascular outcomes, mortality, and cancer per 1.0 mmol/L reduction in LDL cholesterol.
What was found
Mean 1-year LDL cholesterol differences ranged from 0.35 to 1.77 mmol/L (mean 1.09 mmol/L). Across follow-up (8,186 deaths, 14,348 major vascular events, and 5,103 cancer cases): - All-cause mortality decreased by 12% per 1.0 mmol/L LDL reduction (RR 0.88, 95% CI 0.84–0.91; p<0.0001), driven by a 19% reduction in coronary mortality (RR 0.81, 95% CI 0.76–0.85; p<0.0001). Non-coronary vascular mortality (RR 0.93, p=0.2) and non-vascular mortality (RR 0.95, p=0.1) reductions were non-significant. - Major vascular events decreased by 21% (RR 0.79, 95% CI 0.77–0.81; p<0.0001), encompassing reductions in myocardial infarction or coronary death (RR 0.77, 95% CI 0.74–0.80), coronary revascularisation (RR 0.76, 95% CI 0.73–0.80), and stroke (RR 0.83, 95% CI 0.78–0.88; all p<0.0001). - Absolute 5-year event reductions were 48 per 1000 participants (95% CI 39–57) in individuals with baseline coronary heart disease versus 25 per 1000 (95% CI 19–31) in those without. - Statin therapy was not associated with increased overall cancer incidence (RR 1.00, 95% CI 0.95–1.06; p=0.9) or site-specific cancer.
Why it matters
This meta-analysis establishes that statins reliably lower vascular morbidity and all-cause mortality proportionally to the absolute magnitude of LDL cholesterol reduction, with absolute benefit scaling with baseline vascular risk.
Limits
The mean follow-up was limited to 5 years, leaving ultra-long-term outcomes unassessed. The abstract does not report non-cancer safety endpoints (such as myopathy, liver dysfunction, or new-onset diabetes), drug-specific differences among individual statins, or full demographic breakdowns.
Cited by
- supports Lowering elevated blood pressure and treating high cholesterol reduces the risk of heart attacks and adverse cardiovascular outcomes.