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

Mihaylova, B. et al. (2012) 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, 380(9841), pp. 581-590. (doi: 10.1016/S0140-6736(12)60367-5)

Full text not currently available from Enlighten.

Abstract

<p>Background: Statins reduce LDL cholesterol and prevent vascular events, but their net effects in people at low risk of vascular events remain uncertain.</p> <p>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.</p> <p>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.</p> <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.</p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Macfarlane, Professor Peter and Shepherd, Prof James and Ford, Professor Ian and Packard, Professor Chris and Cobbe, Professor Stuart
Authors: Mihaylova, B., Emberson, J., Blackwell, L., Keech, A., Simes, J., Barnes, E.H., Voysey, M., Gray, A., Collins, R., Baigent, C., de Lemos, J., Braunwald, E., Blazing, M., Murphy, S., Downs, J.R., Gotto, A., Clearfield, M., Holdaas, H., Gordon, D., Davis, B., Koren, M., Dahlof, B., Polter, N., Sever, P., Knopp, R.H., Fellstrom, B., Holdaas, H., Jardine, A., Schmieder, R., Zannad, F., Goldbourt, U., Kaplinksy, E., Colhoun, H.M., Betteridge, D.J., Durrington, P.N., Hitman, G.A., Fuller, J., Neil, A., Wanner, C., Krane, V., Sacks, F., Moye, L., Pfeffer, M., Hawkins, C.M., Braunwald, E., Kjekshus, J., Wedel, H., Wikstrand, J., Barter, P., Keech, A., Tavazzi, L., Maggioni, A., Marchioli, R., Tognoni, G., Franzosi, M.G., Maggioni, A., Bloomfield, H., Robin, S., Collins, R., Armitage, J., Keech, A., Parish, S., Peto, R., Sleight, P., Pedersen, T.R., Ridker, P.M., Holman, R., Meade, T., Simes, J., Keech, A., MacMahon, S., Marschner, I., Tonkin, A., Shaw, J., Serruys, P.W., Nakamura, H., Knatterud, G., Furberg, C., Byington, R., Macfarlane, P., Cobbe, S., Ford, I., Murphy, M., Blauw, G.J., Packard, C., Shepherd, J., Kjekshus, J., Pedersen, T., Wilhelmsen, L., Braunwald, E., Cannon, C., Murphy, S., Collins, R., Armitage, J., Bowman, L., Parish, S., Peto, R., Sleight, P., Baigent, C., Landray, M., Collins, R., La Rosa, J., Rossouw, J., Probstfeild, J., Shepherd, J., Cobbe, S., Macfarlane, P., and Ford, I.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Lancet
Publisher:The Lancet Publishing Group
ISSN:0140-6736
ISSN (Online):1474-547X

University Staff: Request a correction | Enlighten Editors: Update this record