Dipyridamole in prevention of stroke

With respect to the use of the combination of modified-release dipyridamole and aspirin and place in management following an ischaemic stroke or a transient ischaemic attack (TIA), NICE have suggested that (1):

• long-term antiplatelet treatment following an ischaemic stroke:
  
  
  • first-line treatment
    • clopidogrel is recommended as first-line treatment
      
      
  • second line treatment
    • combination of modified-release (MR) dipyridamole and aspirin is for people who have had an ischaemic stroke only if clopidogrel is contraindicated or not tolerated - treatment with modified-release dipyridamole in combination with aspirin for people who have had an ischaeminic stroke is no longer limited to two years' duration
      
      
  • third line treatment
    • modified-release dipyridamole alone is recommended as an option to prevent occlusive vascular events for people who have had an ischaemic stroke only if aspirin and clopidogrel are contraindicated or not tolerated
      
      
  • with respect to antiplatelet therapy following a TIA:
    
    
    • first line treatment
      • combination of modified-release (MR) dipyridamole and aspirin is for people who have had an ischaemic stroke only if clopidogrel is contraindicated or not tolerated - treatment with modified-release dipyridamole in combination with aspirin for people who have had a TIA is no longer limited to two years' duration
        
        
    • second line treatment
      • modified-release dipyridamole alone is recommended as an option to prevent occlusive vascular events for people who have had a transient ischaemic attack only if aspirin is contraindicated or not tolerated

Evidence relating to combination of aspirin and dipyridamole in the prevention of major vascular events in patients with a history of cerebrovascular disease.

• the meta-analysis by Leonardi-Bee et al suggests that a combination of dipyridamole and aspirin is significantly, but marginally, more effective than aspirin in preventing major vascular events:
  • risk of recurrent stroke was reduced if used combination of dipyridamole and aspirin (Odds Ratio (OR) 0.78, CI 0.65-0.93) (2)
  • the combination of aspirin and dipyridamole also significantly reduced the composite outcome of nonfatal stroke, nonfatal myocardial infarction, and vascular death as compared with aspirin alone (OR, 0.84; 95% CI, 0.72 to 0.97), dipyridamole alone (OR, 0.76; 95% CI, 0.64 to 0.90), or control (OR, 0.66; 95% CI, 0.57 to 0.75). Vascular death was not altered in any group
  • it is important however to note that the positive result from this meta-analysis is significantly driven by a single randomised controlled trial, the European Stroke Prevention Study 2 (3)
  • the study authors concluded that, in patients with a history of ischaemic cerebrovascular disease, dipyridamole given with or without aspirin reduces the risk of recurrent stroke
• the more recent ESPRIT study also supports the use of a combination of dipyridamole and aspirin in patients with a history of cerebrovascular disease (4)
• Verro P et al undertook a meta-analysis and found that (5):
  • combination of aspirin plus dipyridamole is more effective than aspirin alone in preventing stroke and other serious vascular events in patients with minor stroke and TIAs
  • risk reduction was greater and statistically significant for studies using primarily extended release dipyridamole, which may reflect a true pharmacological effect or lack of statistical power in studies using immediate release dipyridamole

Reference:

• 1. NICE (December 2010).Clopidogrel and modified-release dipyridamole for the prevention of occlusive vascular events
• 2. Leonardi-Bee J et al. Dipyridamole for preventing recurrent ischaemic stroke and other vascular events: a meta-analysis of individual patient data from randomized controlled trials. Stroke 2005; 36:162-8.
• 3. Diener HC et al. European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996;143:1-13
• 4. 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.
• 5. Verro P et al. Aspirin plus dipyridamole versus aspirin for prevention of vascular events after stroke or TIA: a meta-analysis. Stroke. 2008 Apr;39(4):1358-63