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

Abstract

Background There has been debate about whether statin therapy is as effective in women as men, especially for primary prevention. Methods Meta‐analyses were performed on data from 22 trials of statin therapy vs. control (n=134 537) and five trials of more intensive vs. 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 using a Cox model that adjusted for non‐gender differences. For subgroup analyses, 99% confidence intervals were used to make allowance for the multiplicity of comparisons. Findings Overall, 46675 (27%) of 174,149 randomised 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 ~1∙1mmol/L in statin vs. control trials and ~0∙5mmol/L in more vs. less trials). The proportional reductions per 1∙0 mmol/L reduction in LDL cholesterol in major vascular events were similar in women (RR 0∙84, 99% CI 0∙78‐0∙91) and men (RR 0∙78, 99% CI 0∙75‐0∙81), both overall (adjusted p value for heterogeneity by gender=0∙33) and among those at <10% predicted 5‐year risk (adjusted heterogeneity p=0∙11). Likewise, the proportional reductions in major coronary events, coronary revascularisation and stroke did not differ by gender. Since there were similar proportional reductions in vascular mortality in women (RR 0∙92, 99% CI 0∙82‐1∙03) and men (RR 0∙87, 99% CI 0∙82‐0∙92) (adjusted heterogeneity p=0∙84), but no apparent effect on non‐vascular deaths in either sex, all‐cause mortality was reduced in both women (RR 0∙91, 99% CI 0∙84‐0∙99) and men (RR 0∙90, 99% CI 0∙86‐0∙95). Interpretation Other things being equal, statin therapy is of comparable effectiveness for the prevention of major vascular events in women as in men, even among those at low risk of vascular disease.