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

TY - JOUR

T1 - 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

AU - Mihaylova, B.

AU - Emberson, J.

AU - Blackwell, L.

AU - Keech, A.

AU - Simes, J.

AU - Barnes, E. H.

AU - Voysey, M.

AU - Gray, A.

AU - Collins, R.

AU - Baigent, C.

AU - de Lemos, J.

AU - Braunwald, E.

AU - Blazing, M.

AU - Murphy, S.

AU - Downs, J. R.

AU - Gotto, A.

AU - Clearfield, M.

AU - Holdaas, H.

AU - Gordon, D.

AU - Davis, B.

AU - Koren, M.

AU - Dahlof, B.

AU - Poulter, N.

AU - Sever, P.

AU - Knopp, R. H.

AU - Fellstrom, B.

AU - Jardine, A.

AU - Schmieder, R.

AU - Zannad, F.

AU - Goldbourt, U.

AU - Kaplinsky, E.

AU - Colhoun, H. M.

AU - Betteridge, D. J.

AU - Durrington, P. N.

AU - Hitman, G. A.

AU - Fuller, J.

AU - Neil, A.

AU - Wanner, C.

AU - Krane, V.

AU - Sacks, F.

AU - Moye, L.

AU - Pfeffer, M.

AU - Hawkins, C. M.

AU - Kjekshus, J.

AU - Wedel, H.

AU - Wikstrand, J.

AU - Barter, P.

AU - Tavazzi, L.

AU - Maggioni, A.

AU - Marchioli, R.

AU - Cholesterol Treatment Trialists

PY - 2012

Y1 - 2012

N2 - 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, pInterpretation 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.

AB - 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, pInterpretation 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.

KW - MYOCARDIAL-INFARCTION

KW - FOLLOW-UP

KW - SCANDINAVIAN SIMVASTATIN SURVIVAL

KW - PLACEBO-CONTROLLED TRIAL

KW - CARDIOVASCULAR-DISEASE

KW - PRIMARY PREVENTION

KW - DIABETES-MELLITUS

KW - HIGH-DOSE ATORVASTATIN

KW - TREATMENT PANEL-III

KW - CORONARY-HEART-DISEASE

U2 - 10.1016/S0140-6736(12)60367-5

DO - 10.1016/S0140-6736(12)60367-5

M3 - Article

SN - 0140-6736

VL - 380

SP - 581

EP - 590

JO - Lancet

JF - Lancet

IS - 9841

ER -