ArticlesEfficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174 000 participants in 27 randomised trials
Introduction
There is general agreement that statins reduce both cardiovascular events and mortality,1, 2, 3, 4 but uncertainty remains regarding the extent of their effectiveness in women compared with men,5 especially for primary prevention.5, 6, 7, 8, 9, 10, 11 Few studies have reported independently significant cardiovascular benefits in women,5, 12, 13, 14, 15 and much of the resulting uncertainty has been attributed to the under-representation of women in statin trials and a lack of sex-specific analyses in cardiovascular research.16, 17
Previous meta-analyses of the effects of statin therapy in women have reached conflicting conclusions. The authors of a 2010 meta-analysis concluded that, among individuals without known cardiovascular disease, statins might not be as effective in women as in men,10 whereas those of a more recent meta-analysis in 2012 (which included mainly patients receiving statins for primary prevention, but also included some patients receiving statins for secondary prevention) concluded that statins are effective in both sexes.15 Investigators in both studies, however, were able to access information only from a subset of the relevant trials and used published data, thereby limiting the reliability of their findings. Perhaps as a result of this uncertainty, a recent review concluded that a large trial of statin therapy for primary prevention in women is needed.11
The Cholesterol Treatment Trialists' (CTT) Collaboration has previously reported meta-analyses of individual data from 22 trials of standard statin regimens versus control and five trials of more-intensive (ie, higher dose) versus less-intensive (ie, lower dose) regimens; findings from these analyses showed that the proportional benefits of statin therapy for major vascular events were similar irrespective of baseline risk of vascular disease.4 In that study, findings from a subsidiary analysis suggested that the proportional effects of statins on major vascular events did not differ in women and men of equivalent baseline risk of vascular disease. The purpose of the present meta-analysis is to provide a more detailed assessment of the effects of statin therapy on particular vascular and non-vascular outcomes in men and women in the settings of both primary and secondary prevention.
Section snippets
Study design and outcomes
We did a meta-analysis of studies included in the CTT Collaboration database reported up to 2010; the database includes trials of statin therapy versus control and trials that compared statin regimens of differing intensity. A protocol for the CTT Collaboration was agreed in November, 1994, before the results of any of the relevant trials became available.18 Randomised trials were eligible for inclusion if the main effect of at least one of the trial interventions was to reduce LDL cholesterol,
Results
Individual participant data were available from 27 trials of statin therapy: 22 trials examining statin therapy versus control, and five trials examining more-intensive statin therapy versus less-intensive therapy (table 1).2, 23 The median duration of follow-up among survivors was 4·9 years (IQR 4·5–5·3), ranging from 2·0 years20, 24, 25 to 7·0 years.26 Among all trials, 46 675 (26·8%) of 174 149 randomly assigned participants were women. Compared with men, women were older (mean age 65·1 vs
Discussion
To our knowledge, this analysis of individual patient data from more than 174 000 people represents the largest meta-analysis to date comparing statin efficacy by sex, and is the only such analysis to adjust in detail for cardiovascular risk (panel). It is widely accepted that reduction of LDL cholesterol with statin therapy reduces the risk of major coronary events, coronary revascularisation, and ischaemic stroke, and that the absolute benefits of statin therapy are determined chiefly by the
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Collaborators are listed at the end of the report