Aspirin: not licensed for primary prevention of thrombotic vascular disease

In the UK, low-dose aspirin is licensed for prevention of thrombotic cerebrovascular or cardiovascular disease only in those who already have vascular disease—ie, secondary prevention.

From:
Medicines and Healthcare products Regulatory Agency
Published
3 October 2009
Therapeutic area:
Cardiovascular disease and lipidology

Article date: 3 October 2009

Two recent studies have looked at the use of low-dose aspirin in the prevention of heart attacks and strokes in people without a history of vascular disease—ie, primary prevention. Both studies found that the risk of having a major bleed—gastrointestinal bleeding is a known adverse effect of aspirin—outweighed any vascular benefit.

In the UK, low-dose aspirin is licensed for prevention of thrombotic cerebrovascular or cardiovascular disease only in those who already have vascular disease—ie, secondary prevention. Although aspirin is used in primary prevention, this is not a licensed indication.

Recent evidence supporting the current licensed indications for aspirin

AAA study

The Aspirin for Asymptomatic Atherosclerosis trialists at the University of Edinburgh recently reported[footnote 1] the outcome of their randomised study at the European Society of Cardiology Congress in Barcelona, Spain. Between 1998 and 2001, 3350 people in Scotland were recruited who were asymptomatic but at high risk of vascular disease. Participants were randomly assigned aspirin (100 mg/day) or matching placebo, with a mean follow-up of 8·2 years. The primary endpoint was a composite of initial coronary event or stroke or revascularisation (non-fatal or fatal).

For the primary endpoint, no significant difference was found between those allocated aspirin or placebo (181 events vs 176 events; hazard ratio 1·03 [95% CI 0·84–1·27]).

An initial event of major haemorrhage requiring hospital admission occurred in 34 (2%) patients in the aspirin group and in 20 (1·2%) in the placebo group (hazard ratio 1·71[0·99–2·97]). This study therefore found no benefit of aspirin use and an increased risk of serious bleeding in asymptomatic individuals.

ATT collaboration

The Antithrombotic Trialists Collaboration at the University of Oxford did a metaanalysis[footnote 2] to investigate the effect of long-term, low-dose aspirin on the prevention of serious vascular events (ie, heart attack, stroke, or vascular death) and the risk of major bleeds in primary and secondary prevention.

The analysis looked at six primary-prevention trials (95 000 people at low average risk) and 16 secondary-prevention trials (17 000 people at high average risk), which all compared aspirin with a control. In the primary-prevention trials, aspirin reduced serious vascular events by 12% per year compared with no aspirin (0·51% vs 0·57%; p<0·0001), but significantly increased major bleeds (although they remained uncommon: 0·1% per year with aspirin vs 0·07% per year without aspirin; p<0·0001). In the secondary-prevention trials, aspirin reduced serious vascular events by 22% per year compared with no aspirin (6·7% vs 8·2%; p<0·0001) and had a similar effect on major bleeds.

The results of this analysis suggest that aspirin has substantial overall benefit in secondary prevention because it reduces serious cardiovascular events by much more than it increases the risk of major bleeds. However, in primary prevention the absolute risk of a serious vascular event is far lower than in secondary prevention and any vascular benefit of aspirin is likely to be at least partly offset by the small increase in serious bleeding events.

Advice for healthcare professionals:

  • The results of these recent studies lend support to the licensed indications for aspirin in secondary prevention of vascular events only
  • Aspirin is not licensed for the primary prevention of vascular events. If aspirin is used in primary prevention, the balance of benefits and risks should be considered for each individual, particularly the presence of risk factors for vascular disease (including conditions such as diabetes) and the risk of gastrointestinal bleeding

Further information on prescribers’ responsibilities regarding use of unlicensed medicines or off-label use of medicines.

  1. Access the abstract, session number 175–76 (accessed Sept 7, 2009). ↩

  2. See Lancet 2009; 373: 1821–22 ↩

Published 3 October 2009