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

B. Mihaylova, J. Emberson, L. Blackwell, A. Keech, J. Simes, E. H. Barnes, M. Voysey, A. Gray, R. Collins, C. Baigent, J. De Lemos, E. Braunwald, M. Blazing, S. Murphy, John R Downs, A. Gotto, M. Clearfield, H. Holdaas, D. Gordon, B. DavisM. Koren, B. Dahlof, N. Poulter, P. Sever, R. H. Knopp, B. Fellstrom, H. Holdaas, A. Jardine, R. Schmieder, F. Zannad, U. Goldbourt, E. Kaplinsky, H. M. Colhoun, D. J. Betteridge, P. N. Durrington, G. A. Hitman, J. Fuller, A. Neil, C. Wanner, V. Krane, F. Sacks, L. Moye, M. Pfeffer, C. M. Hawkins, E. Braunwald, J. Kjekshus, H. Wedel, J. Wikstrand, P. Barter, A. Keech, L. Tavazzi, A. Maggioni, R. Marchioli, G. Tognoni, M. G. Franzosi, A. Maggioni, H. Bloomfield, S. Robins, R. Collins, J. Armitage, A. Keech, S. Parish, R. Peto, P. Sleight, T. R. Pedersen, P. M. Ridker, R. Holman, T. Meade, J. Simes, A. Keech, S. MacMahon, I. Marschner, A. Tonkin, J. Shaw, P. W. Serruys, H. Nakamura, G. Knatterud, C. Furberg, R. Byington, P. MacFarlane, S. Cobbe, I. Ford, M. Murphy, G. J. Blauw, C. Packard, J. Shepherd, J. Kjekshus, T. Pedersen, L. Wilhelmsen, E. Braunwald, C. Cannon, S. Murphy, R. Collins, J. Armitage, L. Bowman, S. Parish, R. Peto, P. Sleight, M. Landray, R. Collins, J. La Rosa, J. Rossouw, J. Probstfi Eld, J. Shepherd, S. Cobbe, P. MacFarlane, I. Ford, M. Flather, J. Kastelein, C. Newman, C. Shear, J. Tobert, J. Varigos, H. White, S. Yusuf, M. Mellies, M. McGovern, J. Barclay, R. Belder, Merck Y. Mitchel, T. Musliner, J. C. Ansquer, Bayer M. Llewellyn, Novartis Pharma, M. Bortolini, G. Brandrup-Wognsen, B. Bryzinski, G. Olsson, J. Pears, D. DeMicco, E. H. Barnes, A. Baxter, N. Bhala, L. Blackwell, G. Buck, R. Collins, J. Emberson, W. G. Herrington, L. E. Holland, P. M. Kearney, A. Keech, A. Kirby, D. A. Lewis, I. Marschner, C. Pollicino, C. Reith, J. Simes, T. Sourjina

Research output: Contribution to journalArticle

1384 Citations (Scopus)

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 benefi t 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.

Original languageEnglish (US)
Pages (from-to)581-590
Number of pages10
JournalThe Lancet
Volume380
Issue number9841
DOIs
StatePublished - Aug 2012
Externally publishedYes

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Vascular Diseases
LDL Cholesterol
Meta-Analysis
Blood Vessels
Therapeutics
Mortality
Stroke
Guidelines
Risk Reduction Behavior
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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.; 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, John R; Gotto, A.; Clearfield, M.; Holdaas, H.; Gordon, D.; Davis, B.; Koren, M.; Dahlof, B.; Poulter, N.; Sever, P.; Knopp, R. H.; Fellstrom, B.; Holdaas, H.; Jardine, A.; Schmieder, R.; Zannad, F.; Goldbourt, U.; Kaplinsky, 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.; Robins, 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.; Landray, M.; Collins, R.; La Rosa, J.; Rossouw, J.; Probstfi Eld, J.; Shepherd, J.; Cobbe, S.; MacFarlane, P.; Ford, I.; Flather, M.; Kastelein, J.; Newman, C.; Shear, C.; Tobert, J.; Varigos, J.; White, H.; Yusuf, S.; Mellies, M.; McGovern, M.; Barclay, J.; Belder, R.; Mitchel, Merck Y.; Musliner, T.; Ansquer, J. C.; Llewellyn, Bayer M.; Pharma, Novartis; Bortolini, M.; Brandrup-Wognsen, G.; Bryzinski, B.; Olsson, G.; Pears, J.; DeMicco, D.; Barnes, E. H.; Baxter, A.; Bhala, N.; Blackwell, L.; Buck, G.; Collins, R.; Emberson, J.; Herrington, W. G.; Holland, L. E.; Kearney, P. M.; Keech, A.; Kirby, A.; Lewis, D. A.; Marschner, I.; Pollicino, C.; Reith, C.; Simes, J.; Sourjina, T.

In: The Lancet, Vol. 380, No. 9841, 08.2012, p. 581-590.

Research output: Contribution to journalArticle

Mihaylova, B, Emberson, J, Blackwell, L, Keech, A, Simes, J, Barnes, EH, Voysey, M, Gray, A, Collins, R, Baigent, C, De Lemos, J, Braunwald, E, Blazing, M, Murphy, S, Downs, JR, Gotto, A, Clearfield, M, Holdaas, H, Gordon, D, Davis, B, Koren, M, Dahlof, B, Poulter, N, Sever, P, Knopp, RH, Fellstrom, B, Holdaas, H, Jardine, A, Schmieder, R, Zannad, F, Goldbourt, U, Kaplinsky, E, Colhoun, HM, Betteridge, DJ, Durrington, PN, Hitman, GA, Fuller, J, Neil, A, Wanner, C, Krane, V, Sacks, F, Moye, L, Pfeffer, M, Hawkins, CM, Braunwald, E, Kjekshus, J, Wedel, H, Wikstrand, J, Barter, P, Keech, A, Tavazzi, L, Maggioni, A, Marchioli, R, Tognoni, G, Franzosi, MG, Maggioni, A, Bloomfield, H, Robins, S, Collins, R, Armitage, J, Keech, A, Parish, S, Peto, R, Sleight, P, Pedersen, TR, Ridker, PM, Holman, R, Meade, T, Simes, J, Keech, A, MacMahon, S, Marschner, I, Tonkin, A, Shaw, J, Serruys, PW, Nakamura, H, Knatterud, G, Furberg, C, Byington, R, MacFarlane, P, Cobbe, S, Ford, I, Murphy, M, Blauw, GJ, 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, Landray, M, Collins, R, La Rosa, J, Rossouw, J, Probstfi Eld, J, Shepherd, J, Cobbe, S, MacFarlane, P, Ford, I, Flather, M, Kastelein, J, Newman, C, Shear, C, Tobert, J, Varigos, J, White, H, Yusuf, S, Mellies, M, McGovern, M, Barclay, J, Belder, R, Mitchel, MY, Musliner, T, Ansquer, JC, Llewellyn, BM, Pharma, N, Bortolini, M, Brandrup-Wognsen, G, Bryzinski, B, Olsson, G, Pears, J, DeMicco, D, Barnes, EH, Baxter, A, Bhala, N, Blackwell, L, Buck, G, Collins, R, Emberson, J, Herrington, WG, Holland, LE, Kearney, PM, Keech, A, Kirby, A, Lewis, DA, Marschner, I, Pollicino, C, Reith, C, Simes, J & Sourjina, T 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', The Lancet, vol. 380, no. 9841, pp. 581-590. https://doi.org/10.1016/S0140-6736(12)60367-5
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, John R ; Gotto, A. ; Clearfield, M. ; Holdaas, H. ; Gordon, D. ; Davis, B. ; Koren, M. ; Dahlof, B. ; Poulter, N. ; Sever, P. ; Knopp, R. H. ; Fellstrom, B. ; Holdaas, H. ; Jardine, A. ; Schmieder, R. ; Zannad, F. ; Goldbourt, U. ; Kaplinsky, 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. ; Robins, 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. ; Landray, M. ; Collins, R. ; La Rosa, J. ; Rossouw, J. ; Probstfi Eld, J. ; Shepherd, J. ; Cobbe, S. ; MacFarlane, P. ; Ford, I. ; Flather, M. ; Kastelein, J. ; Newman, C. ; Shear, C. ; Tobert, J. ; Varigos, J. ; White, H. ; Yusuf, S. ; Mellies, M. ; McGovern, M. ; Barclay, J. ; Belder, R. ; Mitchel, Merck Y. ; Musliner, T. ; Ansquer, J. C. ; Llewellyn, Bayer M. ; Pharma, Novartis ; Bortolini, M. ; Brandrup-Wognsen, G. ; Bryzinski, B. ; Olsson, G. ; Pears, J. ; DeMicco, D. ; Barnes, E. H. ; Baxter, A. ; Bhala, N. ; Blackwell, L. ; Buck, G. ; Collins, R. ; Emberson, J. ; Herrington, W. G. ; Holland, L. E. ; Kearney, P. M. ; Keech, A. ; Kirby, A. ; Lewis, D. A. ; Marschner, I. ; Pollicino, C. ; Reith, C. ; Simes, J. ; Sourjina, T. / 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. In: The Lancet. 2012 ; Vol. 380, No. 9841. pp. 581-590.
@article{3dbf9e43dcf942798bd6fbbf2d968ab0,
title = "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",
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 benefi t 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.",
author = "B. Mihaylova and J. Emberson and L. Blackwell and A. Keech and J. Simes and Barnes, {E. H.} and M. Voysey and A. Gray and R. Collins and C. Baigent and {De Lemos}, J. and E. Braunwald and M. Blazing and S. Murphy and Downs, {John R} and A. Gotto and M. Clearfield and H. Holdaas and D. Gordon and B. Davis and M. Koren and B. Dahlof and N. Poulter and P. Sever and Knopp, {R. H.} and B. Fellstrom and H. Holdaas and A. Jardine and R. Schmieder and F. Zannad and U. Goldbourt and E. Kaplinsky and Colhoun, {H. M.} and Betteridge, {D. J.} and Durrington, {P. N.} and Hitman, {G. A.} and J. Fuller and A. Neil and C. Wanner and V. Krane and F. Sacks and L. Moye and M. Pfeffer and Hawkins, {C. M.} and E. Braunwald and J. Kjekshus and H. Wedel and J. Wikstrand and P. Barter and A. Keech and L. Tavazzi and A. Maggioni and R. Marchioli and G. Tognoni and Franzosi, {M. G.} and A. Maggioni and H. Bloomfield and S. Robins and R. Collins and J. Armitage and A. Keech and S. Parish and R. Peto and P. Sleight and Pedersen, {T. R.} and Ridker, {P. M.} and R. Holman and T. Meade and J. Simes and A. Keech and S. MacMahon and I. Marschner and A. Tonkin and J. Shaw and Serruys, {P. W.} and H. Nakamura and G. Knatterud and C. Furberg and R. Byington and P. MacFarlane and S. Cobbe and I. Ford and M. Murphy and Blauw, {G. J.} and C. Packard and J. Shepherd and J. Kjekshus and T. Pedersen and L. Wilhelmsen and E. Braunwald and C. Cannon and S. Murphy and R. Collins and J. Armitage and L. Bowman and S. Parish and R. Peto and P. Sleight and M. Landray and R. Collins and {La Rosa}, J. and J. Rossouw and {Probstfi Eld}, J. and J. Shepherd and S. Cobbe and P. MacFarlane and I. Ford and M. Flather and J. Kastelein and C. Newman and C. Shear and J. Tobert and J. Varigos and H. White and S. Yusuf and M. Mellies and M. McGovern and J. Barclay and R. Belder and Mitchel, {Merck Y.} and T. Musliner and Ansquer, {J. C.} and Llewellyn, {Bayer M.} and Novartis Pharma and M. Bortolini and G. Brandrup-Wognsen and B. Bryzinski and G. Olsson and J. Pears and D. DeMicco and Barnes, {E. H.} and A. Baxter and N. Bhala and L. Blackwell and G. Buck and R. Collins and J. Emberson and Herrington, {W. G.} and Holland, {L. E.} and Kearney, {P. M.} and A. Keech and A. Kirby and Lewis, {D. A.} and I. Marschner and C. Pollicino and C. Reith and J. Simes and T. Sourjina",
year = "2012",
month = "8",
doi = "10.1016/S0140-6736(12)60367-5",
language = "English (US)",
volume = "380",
pages = "581--590",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",
number = "9841",

}

TY - JOUR

T1 - The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease

T2 - 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, John 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 - Holdaas, H.

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 - Braunwald, E.

AU - Kjekshus, J.

AU - Wedel, H.

AU - Wikstrand, J.

AU - Barter, P.

AU - Keech, A.

AU - Tavazzi, L.

AU - Maggioni, A.

AU - Marchioli, R.

AU - Tognoni, G.

AU - Franzosi, M. G.

AU - Maggioni, A.

AU - Bloomfield, H.

AU - Robins, S.

AU - Collins, R.

AU - Armitage, J.

AU - Keech, A.

AU - Parish, S.

AU - Peto, R.

AU - Sleight, P.

AU - Pedersen, T. R.

AU - Ridker, P. M.

AU - Holman, R.

AU - Meade, T.

AU - Simes, J.

AU - Keech, A.

AU - MacMahon, S.

AU - Marschner, I.

AU - Tonkin, A.

AU - Shaw, J.

AU - Serruys, P. W.

AU - Nakamura, H.

AU - Knatterud, G.

AU - Furberg, C.

AU - Byington, R.

AU - MacFarlane, P.

AU - Cobbe, S.

AU - Ford, I.

AU - Murphy, M.

AU - Blauw, G. J.

AU - Packard, C.

AU - Shepherd, J.

AU - Kjekshus, J.

AU - Pedersen, T.

AU - Wilhelmsen, L.

AU - Braunwald, E.

AU - Cannon, C.

AU - Murphy, S.

AU - Collins, R.

AU - Armitage, J.

AU - Bowman, L.

AU - Parish, S.

AU - Peto, R.

AU - Sleight, P.

AU - Landray, M.

AU - Collins, R.

AU - La Rosa, J.

AU - Rossouw, J.

AU - Probstfi Eld, J.

AU - Shepherd, J.

AU - Cobbe, S.

AU - MacFarlane, P.

AU - Ford, I.

AU - Flather, M.

AU - Kastelein, J.

AU - Newman, C.

AU - Shear, C.

AU - Tobert, J.

AU - Varigos, J.

AU - White, H.

AU - Yusuf, S.

AU - Mellies, M.

AU - McGovern, M.

AU - Barclay, J.

AU - Belder, R.

AU - Mitchel, Merck Y.

AU - Musliner, T.

AU - Ansquer, J. C.

AU - Llewellyn, Bayer M.

AU - Pharma, Novartis

AU - Bortolini, M.

AU - Brandrup-Wognsen, G.

AU - Bryzinski, B.

AU - Olsson, G.

AU - Pears, J.

AU - DeMicco, D.

AU - Barnes, E. H.

AU - Baxter, A.

AU - Bhala, N.

AU - Blackwell, L.

AU - Buck, G.

AU - Collins, R.

AU - Emberson, J.

AU - Herrington, W. G.

AU - Holland, L. E.

AU - Kearney, P. M.

AU - Keech, A.

AU - Kirby, A.

AU - Lewis, D. A.

AU - Marschner, I.

AU - Pollicino, C.

AU - Reith, C.

AU - Simes, J.

AU - Sourjina, T.

PY - 2012/8

Y1 - 2012/8

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%, ≥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 benefi t 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%, ≥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 benefi t 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.

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

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

M3 - Article

C2 - 22607822

AN - SCOPUS:84864832599

VL - 380

SP - 581

EP - 590

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 9841

ER -