Should we??

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

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

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 > 20%

SIGN

In doing so, SIGN, like other guidelines tends to assume: 1.

2.

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?

Today...

BMJ 2005 330:1440-41 “

Aspirin for everyone older than 50?”

Antithrombotic Trialists’ Collaboration

 May 2009, Lancet  The authors recognised that existing metanalysis trials didn’t involve details about the individuals in the trial  Therefore, couldn’t look at important separate groups eg. Elderly, men, women, those at “high risk”...

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...

Method

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

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

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

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

• • • • • • • • • • •

Even more...

This risk reduction of events didn’t alter even if you were...

Young Old Fat Thin Male Female Smoker Diabetic Ugly (Just joking) Or “cardiovascular risk of > 20%”

And to rub more salt into the wound...

Nowadays, anyone who is “at risk” is on 1.

Statins (which halve the risk on their own) 2.

Antihypertensives ...which further reduces a patients absolute risk of events...

...without a risk of bleeding...

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...

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

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

So....?

 SIGN haven’t yet changed the guidelines  What do we do in the meantime?

 Would you take Aspirin for Primary Prevention?