Background Statins reduce LDL cholesterol and prevent vascular events, but their net effects in people at low risk of vascular events remain uncertain.
Methods This meta-analysis included individual participant data from 22 trials of statin versus control (n=134 537; mean LDL cholesterol difference 1.08 mmol/L; median follow-up 4.8 years) and five trials of more versus less statin (n=39 612; difference 0.51 mmol/L; 5.1 years). Major vascular events were major coronary events (ie,non-fatal myocardial infarction or coronary death), strokes, or coronary revascularisations. Participants were separated into five categories of baseline 5-year major vascular event risk on control therapy (no statin or low-intensity statin) (= 5% to = 10% to = 20% to = 30%); in each, the rate ratio (RR) per 1.0 mmol/L LDL cholesterol reduction was estimated.
Findings Reduction of LDL cholesterol with a statin reduced the risk of major vascular events (RR 0.79, 95% CI 0.77-0.81, per 1.0 mmol/L reduction), largely irrespective of age, sex, baseline LDL cholesterol or previous vascular disease, and of vascular and all-cause mortality. The proportional reduction in major vascular events was at least as big in the two lowest risk categories as in the higher risk categories (RR per 1.0 mmol/L reduction from lowest to highest risk: 0.62 [99% CI 0.47-0.81], 0.69 [99% CI 0.60-0.79], 0.79 [99% CI 0.74-0.85], 0.81 [99% CI 0.77-0.86], and 0.79 [99% CI 0.74-0.84]; trend p=0.04), which reflected significant reductions in these two lowest risk categories in major coronary events (RR 0.57, 99% CI 0.36-0.89, p=0.0012, and 0.61, 99% CI 0.50-0.74, p
Interpretation In individuals with 5-year risk of major vascular events lower than 10%, each 1 mmol/L reduction in LDL cholesterol produced an absolute reduction in major vascular events of about 11 per 1000 over 5 years. This benefit greatly exceeds any known hazards of statin therapy. Under present guidelines, such individuals would not typically be regarded as suitable for LDL-lowering statin therapy. The present report suggests, therefore, that these guidelines might need to be reconsidered.
- SCANDINAVIAN SIMVASTATIN SURVIVAL
- PLACEBO-CONTROLLED TRIAL
- PRIMARY PREVENTION
- HIGH-DOSE ATORVASTATIN
- TREATMENT PANEL-III