Stroke: dipyridamole with aspirin was better than aspirin alone.

Clinical bottom line (level 1b)

  1. Patients with a transient ischaemic attack or stroke who were given dipyridamole with aspirin were less likely to have another stroke, than those given aspirin alone (NNT = 30 at 2 years) .
  2. There was no clear difference in mortality at two years.
  3. Aspirin alone and dipyridamole alone were both more effective than placebo at decreasing stroke.
Diener et al: Journal of the Neurological Sciences 1996; 143: 1-13
Expires December 2002

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: 59 sites across 13 countries in Europe, between 1989 - 1995

6602 patients (aged mean 67 years, 58% male) recent transient ischaemic attack (clinical neurological symptoms persisting <24 hours) (25%), or stroke (deficit lasting >24 hours) (75%) within the last three months- diagnosed by clinical examination

Excluded if
  • aged <18
  • contraindication to either of treatment drugs: hypersensitivity; recent GI bleed; bleeding disturbances
  • concomitant antiplatelet or anticoagulation treatment


    • Control Group: (n = 1649, 1649 analysed): placebo
    Experimental Group: (n = 1649, 1649 analysed): aspirin 25 mg twice daily
    Experimental Group: (n = 1654, 1654 analysed): dipyridamole retard 200 mg twice daily
    Experimental Group: (n = 1650, 1650 analysed): aspirin and dipyridamole

    99.4% followed for 2 years

    The evidence

    aspirin vs placebo
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    stroke 2 years 250
    (15.2%)    		 206
    (12.5%)    		 18%
    (2% to 31%)    		 2.67%
    (0.31% to 5.02%)    		 37
    (20 to 300)
    death 2 years 202
    (12.3%)    		 182
    (11.0%)    		 10%
    (-9% to 25%)    		 1.21%
    (-0.98% to 3.40%)    		 82
    (NNT = 29 to infinity;
    NNH = 100 to infinity)
    stroke or death 2 years 378
    (22.9%)    		 330
    (20.0%)    		 13%
    (0% to 23%)    		 2.91%
    (0.11% to 5.71%)    		 34
    (18 to 900)

    dipyridamole plus aspirin vs aspirin alone (control)
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    stroke 2 years 206
    (12.5%)    		 157
    (9.52%)    		 24%
    (7% to 37%)    		 2.98%
    (0.84% to 5.11%)    		 34
    (20 to 120)
    death 2 years 182
    (11.0%)    		 185
    (11.2%)    		 -2%
    (-23% to 16%)    		 -0.18%
    (-2.32% to 1.97%)    		 -570
    (NNT = 51 to infinity;
    NNH = 43 to infinity)
    stroke or death 2 years 330
    (20.0%)    		 286
    (17.3%)    		 13%
    (0% to 25%)    		 2.68%
    (0.02% to 5.34%)    		 37
    (19 to 4800)

  • Dipyridamole alone had a similar effect to aspirin.

    • Comments

    1. The EAFT group showed that patients with atrial fibrillation and previous stroke had fewer strokes on warfarin than with aspirin, and these patients were recommended to change from the trial to warfarin.
    2. Compliance was checked by asking the patients if they had taken the medication, pill counting and by a random drug assay.
    3. 438 patients from one centre were excluded before randomisation because of questions being raised over the reliability of the data.
    4. A sustained-release formulation of dipyridamole was used, and the results may not necessarily be generalized to the use of other formulations of dipyridamole.

    Citation

    1. Diener HC, Cunha L, Forbes C, et al: European Stroke Prevention Study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. Journal of the Neurological Sciences 1996; 143: 1-13
    Search Terms: 'Stroke' and 'dipyridamole' and 'randomised controlled trial' in MEDLINE
    Contributor: Nick Shenker and Clare Wotton, October 2000
    Reviewer: Deepak L Bhatt

    Clinical Question.
    Patient TIA or stroke
    Intervention or Exposure dipyridamole plus aspirin
    Comparison aspirin alone
    Outcome stroke, death