Statins and cholesterol

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Statins and cholesterol
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Statins and cholesterol

• There is a strong relationship between total
  serum cholesterol concentration and CVD
• The relationship between total cholesterol, LDL-
  and HDL- cholesterol and the relative risk of CVD
  are similar in people with or without CHD
• The effectiveness of statins in preventing
  cardiovascular events in people with and without
  established CVD is well supported by high quality
  evidence
• A meta-analysis of 14 randomised statin trials
  found that the 5-year incidence of major coronary
  events, coronary revascularisation and stroke was
  reduced by about 20

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MRC/BHF Heart Protection Study of cholesterol
lowering with simvastatin in 20 536 high-risk
individuals


HPS, Lancet 2002
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Statin randomised controlled trials in primary
and secondary prevention populations
30
4S
25
4S
20
LIPID
LIPID
15
Event Rate ()
CARE
HPS
CARE
10
HPS
WOSCOPS
AFCAPS
5
WOSCOPS
AFCAPS
0
80
90
100
110
120
130
140
150
160
170
180
190
200
LDL-C Achieved (mg/dL)
Adapted from Ballantyne CM. Am J Cardiol. 1998
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Randomised trial evidence of benefit of
cholesterol lowering with statinsAbsolute
reduction in LDL cholesterol and
absolutereduction in major cardiac events
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Cholesterol Trialists Collaboration Major events
and mean absolute LDL cholesterol reduction at 1
year Approximately linear relationship between
absolute reduction in LDL cholesterol and the
proportional reduction in coronary and other
events Lancet 2005 366 1267-78 Efficacy and
safety of cholesterol-lowering treatment
prospective meta-analysis of data from 90,056
participants in 14 randomised trials of
statins
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Cholesterol Trialists Collaboration Summary
findings

• The reduction in LDL cholesterol achieved in
  these trials was 0.8 mmol/l on average
• 48 fewer major CV events per 1000 people among
  those with pre-existing CHD at baseline
• 25 fewer major CV events per 1000 in people with
  no history of CHD
• Over average 5 year treatment period (per mmol/l
  LDL cholesterol)
• 12 reduction in all-cause mortality
• 19 reduction in coronary mortality
• 23 reduction in MI or CHD death
• 17 reduction in stroke
• 21 reduction in major vascular events
• No difference in cancer incidence
• Statin therapy can safely reduce 5-year incidence
  of major coronary events, revascularization, and
  stroke by about 20 per mmol/l reduction in LDL
  cholesterol

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Cholesterol Trialists Collaboration5-year
absolute benefits on vascular outcomes per mmol/l
LDL cholesterol reduction in participants with
and without previous MI or CHD
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Higher versus lower intensity statins

• No published randomised trials that have treated
  to a target
• 4 randomised controlled trials compared higher
  versus lower intensity statins in secondary
  prevention populations
• Meta-analyses of these studies found 16
  reduction in cardiac events with an observed LDL
  cholesterol reduction of 0.67 mmol/l, consistent
  with CTC data

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Comments on treating to a LDL cholesterol target
below 2 mmol/l

• Most trials to date have not shown a reduction in
  LDL cholesterol below 2 mmol/l (in only 3 of 20
  trials previously illustrated)
• Trials have strict recruitment criteria, and
  patients with high LDL cholesterol tend to be
  excluded, hence trial populations are not
  representative
• Benefit related to underlying absolute risk
• Greatest benefit in outcomes occurs with initial
  dose
• While there is a near linear relationship between
  log of the risk and cholesterol reduction
  (relative risk reduction remains constant), at
  lower cholesterol levels there is a smaller
  absolute reduction CV and it is absolute risk
  reduction that determines cost-effectiveness

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