Should we??

Aspirin is useful!It is widely used in secondary preventionIt reduces the yearly risk of vascular events

by about a quarterThis corresponds to an absolute reduction of

about 10-20/1000 non fatal events...and a smaller, but definite, reduction in

deathTherefore the increase in major bleeds is a

risk worth taking

SIGNAcknowledges 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%

SIGNIn doing so, SIGN, like other guidelines tends

to assume:1. That the risk of bleeding remains constant

irrespective of the risk of cardiovascular disease

2. ...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’ CollaborationMay 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...

MethodLooked 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

Vs1883 events in 330,000 person years in the

control group

Looking more closelyIn 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 on1.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?