Cholesterol Treatment Trialists' Collaborators meta-analysis 2005

Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins

• a prospective meta-analysis of data from 90 056 individuals in 14 randomised trials of statins was undertaken
• results of meta-analysis:
  • during a mean of 5 years, there were 8186 deaths, 14 348 individuals had major vascular events, and 5103 developed cancer
  • mean LDL cholesterol differences at 1 year ranged from 0·35 mmol/L to 1·77 mmol/L (mean 1·09) in these trials
  • a 12% proportional reduction in all-cause mortality per mmol/L reduction in LDL cholesterol (rate ratio [RR] 0·88, 95% CI 0·84-0·91; p<0·0001)
    • reflected a 19% reduction in coronary mortality (0·81, 0·76-0·85; p<0·0001), and non-significant reductions in non-coronary vascular mortality (0·93, 0·83-1·03; p=0·2) and non-vascular mortality (0·95, 0·90-1·01; p=0·1
    • there were corresponding reductions in myocardial infarction or coronary death (0·77, 0·74-0·80; p<0·0001), in the need for coronary revascularisation (0·76, 0·73-0·80; p<0·0001), in fatal or non-fatal stroke (0·83, 0·78-0·88; p<0·0001), and, combining these, of 21% in any such major vascular event (0·79, 0·77-0·81; p<0·0001)
    • proportional reduction in major vascular events differed significantly (p<0·0001) according to the absolute reduction in LDL cholesterol achieved, but not otherwise
  • benefits were significant within the first year, but were greater in subsequent years
  • the overall reduction of about one fifth per mmol/L LDL cholesterol reduction translated into 48 (95% CI 39-57) fewer participants having major vascular events per 1000 among those with pre-existing CHD at baseline, compared with 25 (19-31) per 1000 among participants with no such history
  • no evidence that statins increased the incidence of cancer overall (1·00, 0·95-1·06; p=0·9) or at any particular site.

Based on this meta-analysis the study authors have suggested that:

• assessment of baseline risk should be based on any type of occlusive vascular event (rather than on coronary events alone), since lowering LDL cholesterol with a statin lowers the risks not just of coronary events but also of revascularisation procedures and of ischaemic strokes
• treatment goals for statin treatment should aim chiefly to achieve substantial absolute reductions in LDL cholesterol (rather than to achieve particular target levels of LDL cholesterol), since the risk reductions are proportional to the absolute LDL cholesterol reductions
• full compliance with available statin regimens can reduce LDL cholesterol by at least 1·5 mmol/L in many circumstances, and hence might be expected to reduce the incidence of major vascular events by about one third

Conclusions:

• the study authors concluded that statin therapy can safely reduce the 5-year incidence of major coronary events, coronary revascularisation, and stroke by about one fifth per mmol/L reduction in LDL cholesterol, largely irrespective of the initial lipid profile or other presenting characteristics
• absolute benefit relates chiefly to an individual's absolute risk of such events and to the absolute reduction in LDL cholesterol achieved
• the study authors suggested that these findings reinforce the need to consider prolonged statin treatment with substantial LDL cholesterol reductions in all patients at high risk of any type of major vascular event

Notes:

• this meta-analysis included data from both primary and secondary prevention trials

Reference:

1. Baigent C et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005 Oct 8;366(9493):1267-78