Efficacy and safety of LDL-lowering therapy among men and women: Meta-analysis of individual data from 174 000 participants in 27 randomised trials

Jordan Fulcher, Rachel O'Connell, Merryn Voysey, Jonathan Emberson, Lisa Blackwell, Borislava Mihaylova, John Simes, Rory Collins, Adrienne Kirby, Helen Colhoun, Eugene Braunwald, John La Rosa, T. R. Pedersen, Andrew Tonkin, Barry Davis, Peter Sleight, Maria Grazia Franzosi, Colin Baigent, Anthony Keech, J. De LemosE. Braunwald, M. Blazing, S. Murphy, J. R. Downs, A. Gotto, M. Clearfield, H. Holdaas, D. Gordon, B. Davis, M. Koren, B. Dahlöf, N. Poulter, P. Sever, R. H. Knopp, B. Fellström, 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. Moyé, 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, C. Baigent, M. Landray, R. Collins, J. La Rosa, J. Rossouw, J. Probstfield, J. Shepherd, S. Cobbe, P. Macfarlane, I. Ford, M. Flather, J. Kastelein, C. Newman, C. Shear, J. Tobert, J. Varigos, H. White, S. Yusuf, E. H. Barnes, A. C. Keech, A. Kirby, I. C. Marschner, J. Simes, C. Baigent, L. Blackwell, R. Collins, J. Emberson, W. G. Herrington, L. E. Holland, B. Mihaylova, C. Reith

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Abstract

Background: Whether statin therapy is as effective in women as in men is debated, especially for primary prevention. We undertook a meta-analysis of statin trials in the Cholesterol Treatment Trialists' (CTT) Collaboration database to compare the effects of statin therapy between women and men. Methods: We performed meta-analyses on data from 22 trials of statin therapy versus control (n=134 537) and five trials of more-intensive versus less-intensive statin therapy (n=39 612). Effects on major vascular events, major coronary events, stroke, coronary revascularisation and mortality were weighted per 1·0 mmol/L reduction in LDL cholesterol and effects in men and women compared with a Cox model that adjusted for non-sex differences. For subgroup analyses, we used 99% CIs to make allowance for the multiplicity of comparisons. Findings 46 675 (27%) of 174 149 randomly assigned participants were women. Allocation to a statin had similar absolute effects on 1 year lipid concentrations in both men and women (LDL cholesterol reduced by about 1·1 mmol/L in statin vs control trials and roughly 0·5 mmol/L for more-intensive vs less-intensive therapy). Women were generally at lower cardiovascular risk than were men in these trials. The proportional reductions per 1·0 mmol/L reduction in LDL cholesterol in major vascular events were similar overall for women (rate ratio [RR] 0·84, 99% CI 0·78-0·91) and men (RR 0·78, 99% CI 0·75-0·81, adjusted p value for heterogeneity by sex=0·33) and also for those women and men at less than 10% predicted 5 year absolute cardiovascular risk (adjusted heterogeneity p=0·11). Likewise, the proportional reductions in major coronary events, coronary revascularisation, and stroke did not differ significantly by sex. No adverse effect on rates of cancer incidence or non-cardiovascular mortality was noted for either sex. These net benefits translated into all-cause mortality reductions with statin therapy for both women (RR 0·91, 99% CI 0·84-0·99) and men (RR 0·90, 99% CI 0·86-0·95; adjusted heterogeneity p=0·43). Interpretation In men and women at an equivalent risk of cardiovascular disease, statin therapy is of similar effectiveness for the prevention of major vascular events.

Original languageEnglish
Pages (from-to)1397-1405
Number of pages9
JournalLancet
Volume385
Issue number9976
DOIs
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Medicine(all)

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    Fulcher, J., O'Connell, R., Voysey, M., Emberson, J., Blackwell, L., Mihaylova, B., Simes, J., Collins, R., Kirby, A., Colhoun, H., Braunwald, E., La Rosa, J., Pedersen, T. R., Tonkin, A., Davis, B., Sleight, P., Franzosi, M. G., Baigent, C., Keech, A., ... Reith, C. (2015). Efficacy and safety of LDL-lowering therapy among men and women: Meta-analysis of individual data from 174 000 participants in 27 randomised trials. Lancet, 385(9976), 1397-1405. https://doi.org/10.1016/S0140-6736(14)61368-4