ESPRIT study

• study design:
  • prospective, randomised controlled trial
  • treatment was open
  • assessment of endpoints was blinded
  • patients (n=2739) were recruited from 79 hospitals in 14 countries within 6 months of a transient ischaemic attack (TIA) or non-disabling stroke of presumed arterial origin
  • patients were assigned aspirin (30–325mg daily, mean 75mg) with or without dipyridamole (200mg twice daily)
    • majority (83%) of the patients allocated dipyridamole received the modified-release formulation
  • follow-up was for up to eight years (mean 3.5 years)
  • primary outcome event was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction (MI), or major bleeding complications
    • primary analysis was by intention to treat
• study results:
  • fewer patients in the aspirin plus dipyridamole group had a primary outcome event compared with those in the aspirin alone group (12.7% vs. 15.7%; hazard ratio [HR] 0.80, 95%CI 0.66–0.98)
    • number needed to treat [NNT] was 33 over 3.5 years
    • annual absolute risk reduction was 0.96% (NNT 104 per year, 95%CI 55-1006)
    • no significant difference in all-cause mortality (aspirin plus dipyridamole 6.8% vs. aspirin alone 7.8%; HR 0.88, 95%CI 0.67–1.17)
  • adverse effects:
    • higher proportion of patients discontinued treatment with the combination than with aspirin alone (34% vs. 13%) - mainly due to adverse effects
      • in 26% of cases headache was at least partly responsible in those who discontinued the combination
      • no statistically significant difference between the incidences of major (combination 3% vs. aspirin alone 4%) or minor (both 12%) bleeding
• the ESPRIT study supports the prescribing of a combination of modified-release dipyridamole and low-dose aspirin for patients who have had a transient ischaemic attack (TIA) or non-disabling ischaemic stroke (2)

Notes:

• there are various limitations with this study (2)
  • over 40% of patients were prescribed 30mg of aspirin, a dose below that currently recommended in UK guidelines
  • study also failed to report or take account of the use of other secondary preventative measures, such as blood pressure control, smoking cessation and lipid-lowering
    • at baseline, proportion of study who smoked (36%), had hypertension (60%) , hyperlipidaemia (46%)

Reference:

1. The ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet 2006;367:1665–73.
2. MeReC Rapid Review (2006);1.