Acetylsalicylic acid + extended-release dipyridamole combination therapy for secondary stroke prevention

Clin Ther. 2008 Jul;30(7):1196-205. doi: 10.1016/s0149-2918(08)80046-x.


Background: Approximately 25% of strokes are recurrent. Antiplatelet therapy is indicated for the prevention of recurrent stroke in patients with a history of noncardioembolic minor stroke or transient ischemic attack (TIA). Although clinicians may choose acetylsalicylic acid (ASA) as first-line therapy for secondary prevention, clinical guidelines and evidence from trials suggest that ASA may not be the most effective strategy.

Objective: The purpose of this review was to discuss results from clinical trials that have compared the efficacy of ASA monotherapy versus ASA + extendedrelease dipyridamole in secondary stroke prevention.

Methods: Relevant randomized experimental and clinical studies in patients with a history of minor stroke or TIA of noncardioembolic etiology were identified using a search of the US National Library of Medicine database, with no limits on publication dates. The primary search terms used were secondary stroke prevention, antiplatelet therapy, acetylsalicylic acid, ASA, aspirin, aspirin + extended-release dipyridamole, and combination therapy.

Results: Early trials of dipyridamole monotherapy or ASA + dipyridamole involved small numbers of patients and found no significant treatment differences. Two major trials that compared ASA monotherapy, dipyridamole monotherapy, and ASA + dipyridamole were identified: the Second European Stroke Prevention Study (ESPS-2) and the European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT). Efficacy measurements in ESPS-2 found that stroke relative risk reductions were 18% (P = 0.013), 16% (P = 0.039), and 37% (P < 0.001), respectively, compared with placebo for a relative risk reduction of 23.1% (P = 0.006) favoring the combination over ASA monotherapy. In ESPRIT, patients who received ASA + dipyridamole had a 20% relative risk reduction versus ASA monotherapy for the composite end point of death from all vascular causes, nonfatal stroke, nonfatal myocardial infarction, or major bleeding complications. In ESPS-2, headache was 5% more common with dual therapy compared with ASA monotherapy. ESPRIT found that combination treatment was not associated with a higher complication rate than ASA monotherapy, but that the rate of withdrawal due to adverse events was higher in the group that received the combination.

Conclusion: Based on the results from these 2 large, randomized trials, ASA + dipyridamole was more effective than ASA monotherapy as first-line therapy for secondary stroke prevention in these patients with a history of minor stroke or TIA of noncardioembolic etiology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aspirin / therapeutic use*
  • Clopidogrel
  • Dipyridamole / therapeutic use*
  • Drug Therapy, Combination
  • Humans
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Practice Guidelines as Topic
  • Secondary Prevention
  • Stroke / prevention & control*
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use


  • Platelet Aggregation Inhibitors
  • Dipyridamole
  • Clopidogrel
  • Ticlopidine
  • Aspirin