Aspirin in Primary Prevention of Cardiovascular Disease

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Aspirin in Primary Prevention of Cardiovascular
Disease

• Should we??
• Victoria Brown

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Aspirin is useful!

• It is widely used in secondary prevention
• It reduces the yearly risk of vascular events by
  about a quarter
• This corresponds to an absolute reduction of
  about 10-20/1000 non fatal events
• ...and a smaller, but definite, reduction in
  death
• Therefore the increase in major bleeds is a risk
  worth taking

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SIGN

• Acknowledges that there is some controversy about
  the use of aspirin in Primary Prevention of
  Cardiovascular disease
• It reduces risk of MI by 30...
• ...but increases risk of haemorrhagic stroke by
  40...
• ...and major GI bleeds by 70
• All cause mortality not affected

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SIGN...

• So, do you wait for a first event? It could be a
  fatal one!
• SIGN conclude that the cut off where the risk
  is worth it...
• ...is a calculated cardiovascular risk of gt 20

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SIGN

• In doing so, SIGN, like other guidelines tends to
  assume
• That the risk of bleeding remains constant
  irrespective of the risk of cardiovascular
  disease
• ...or that it depends on age alone
• But is that justified?

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Today...
BMJ 2005 3301440-41 Aspirin for everyone
older than 50?
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Antithrombotic Trialists Collaboration

• May 2009, Lancet
• The authors recognised that existing metanalysis
  trials didnt involve details about the
  individuals in the trial
• Therefore, couldnt look at important separate
  groups eg. Elderly, men, women, those at high
  risk...

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Aims

• To assess the incidence of serious vascular
  events and major bleeds in primary and secondary
  prevention trials, comparing aspirin with
  controls
• To further analyse the primary prevention trials
  by looking at individual participant data to
  compare the benefits/risks of aspirin in
  prognostically important groups eg. Male v
  Female, old people...

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Method

• Looked at primary and secondary trials to provide
  a comparison
• Analysed individual data
• Six primary prevention trials
• 16 Secondary prevention trials

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Results

• Whether Aspirin is used in primary or secondary
  prevention, the proportion of reduction in major
  coronary events or in stroke is about the same.
• Because patients in the primary prevention group
  are less at risk anyway, the absolute risk is
  therefore much smaller

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Looking more closely...

• Primary prevention trials showed 1671 serious
  vascular events in 330,000 aspirin-person-years
  in the aspirin group
• Vs
• 1883 events in 330,000 person years in the
  control group

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Looking more closely

• In primary prevention, aspirin reduces the rate
  of serious vascular events by 12 (0.51 Vs 0.57
  events per yr)
• This is largely due to the fall in MIs
• Ischaemic strokes largely unchanged
• Overall vascular mortality is unchanged

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Even more...

• This risk reduction of events didnt alter even
  if you were...
• Young
• Old
• Fat
• Thin
• Male
• Female
• Smoker
• Diabetic
• Ugly (Just joking)
• Or cardiovascular risk of gt 20

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And to rub more salt into the wound...

• Nowadays, anyone who is at risk is on
• Statins (which halve the risk on their own)
• Antihypertensives
• ...which further reduces a patients absolute risk
  of events...
• ...without a risk of bleeding...

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So...

• Therefore, adding in aspirin will only give an
  even smaller reduction in the risk of events
• But the bleeding risk will probably remain the
  same!
• Actually, this paper suggests that there are risk
  factors for bleeds Diabetes, Hypertension...

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Caveats

• We might be wrong, because the papers might be
  wrong (ie have underestimated the risk reduction
  of vascular events)
• There might still be a particular group for whom
  aspirin is of net benefit. Eg diabetics without
  vascular disease
• The vast majority of the participants where at
  low risk so the data might not be reliable for
  higher risk groups

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Nailing your colours to the mast!
(Summary)

• In primary prevention, aspirin is of uncertain
  net value as the reduction in occlusive events
  needs to be weighed against the increase in major
  bleeds.
• This is compounded when we treat with other
  risk-lowering drugs

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So....?

• SIGN havent yet changed the guidelines
• What do we do in the meantime?
• Would you take Aspirin for Primary Prevention?