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.

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Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, Voysey M, Gray A, Collins R, Baigent C

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.

Lancet. 2012 Aug 11;380(9841):581-90. doi: 10.1016/S0140-6736(12)60367-5. Epub 2012 May 17.

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22607822 [ View in PubMed
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Abstract

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%, >/=5% to <10%, >/=10% to <20%, >/=20% to <30%, >/=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<0.0001) and in coronary revascularisations (RR 0.52, 99% CI 0.35-0.75, and 0.63, 99% CI 0.51-0.79; both p<0.0001). For stroke, the reduction in risk in participants with 5-year risk of major vascular events lower than 10% (RR per 1.0 mmol/L LDL cholesterol reduction 0.76, 99% CI 0.61-0.95, p=0.0012) was also similar to that seen in higher risk categories (trend p=0.3). In participants without a history of vascular disease, statins reduced the risks of vascular (RR per 1.0 mmol/L LDL cholesterol reduction 0.85, 95% CI 0.77-0.95) and all-cause mortality (RR 0.91, 95% CI 0.85-0.97), and the proportional reductions were similar by baseline risk. There was no evidence that reduction of LDL cholesterol with a statin increased cancer incidence (RR per 1.0 mmol/L LDL cholesterol reduction 1.00, 95% CI 0.96-1.04), cancer mortality (RR 0.99, 95% CI 0.93-1.06), or other non-vascular mortality. 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. FUNDING: British Heart Foundation; UK Medical Research Council; Cancer Research UK; European Community Biomed Programme; Australian National Health and Medical Research Council; National Heart Foundation, Australia.

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