Clinical Question:
Are statins (Simvastatin, Atorvastatin, Rosuvastatin) effective in
preventing coronary artery disease?
Bottom Line:
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. The absolute benefit relates
chiefly to an individual's absolute risk of such events and to the absolute
reduction in LDL cholesterol achieved. 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.
Reference:
Baigent C, Keech A, Kearney PM, et al for the Cholesterol Treatment
Trialists' (CTT) Collaborators. Efficacy and safety of cholesterol-lowering
treatment: prospective meta-analysis of data from 90,056 participants in 14
randomised trials of statins. Lancet 2005;366:1267-78.
Study Design:
Meta-analysis (randomized controlled trials)
Funding:
Industry + govt
Setting:
Outpatient (any)
Synopsis:
Results of previous randomised trials have shown that interventions that
lower LDL cholesterol concentrations can significantly reduce the incidence
of coronary heart disease (CHD) and other major vascular events in a wide
range of individuals. But each separate trial has limited power to assess
particular outcomes or particular categories of participant. A prospective
meta-analysis of data from 90,056 individuals in 14 randomised trials of
statins was done. Weighted estimates were obtained of effects on different
clinical outcomes per 1.0 mmol/L reduction in LDL cholesterol. 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.
There was 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). This 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). The
proportional reduction in major vascular events differed significantly
(p<0.0001) according to the absolute reduction in LDL cholesterol achieved,
but not otherwise. These benefits were significant within the first year,
but were greater in subsequent years. Taking all years together, 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. There was no evidence that
statins increased the incidence of cancer overall (1.00, 0.95-1.06; p=0.9)
or at any particular site.
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