Authors
Diener HC, Cunha CF, Sivenius J, et al.
Title
Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke
References
J Neurol Sci 1996;143:1-13.
Background
The first ESPS study compared dipyridamole 75 mg tid in combination with aspirin 330 mg tid versus placebo for two years in patients who had a prior ischemic stroke or TIA. The combination showed a 38% reduction in recurrent stroke, which was more than seen in other trials comparing ASA alone to placebo. The best dosing of aspirin is not known.
Purpose
To determine the effectiveness and safety of low dose aspirin, of dipyridamole extended release (ER), and the 2 agents in combination (Aggrenox) for the reduction of the risk of subsequent ischemic stroke.
Design
  • Randomized, 2x2 factorial, double-blind, placebo-controlled, multicenter trial
  • 6, 602 patients with prior stroke or TIA within previous 3 months.
Exclusion Criteria
None.
Follow-Up
2 years
Treatment Regimen
Patients were randomized to one of four treatment groups:
  • Aspirin 25 mg bid
  • Dipyridamole extended release 200 mg bid
  • Combination of aspirin/dypyridamole (Aggrenox) 1 capsule bid
  • Placebo
Results
Primary Endpoints: Stroke; death from all causes;stroke and/or death.

Factorial analysis showed that all active arms of the trial significantly decreased the risk of ischemic stroke. There was no significant difference in endpoints when aspirin monotherapy was compared to dipyridamole monotherapy. The combination of aspirin and dipyridamole provided an even greater stroke risk reduction (37%) than placebo. Compared to aspirin, Aggrenox provided a 23% relative risk reduction on the occurrence of stroke.

Factorial analysis showed that compared to placebo, both aspirin and dipyridamole significantly decreased TIA occurrence by 21.9% and 18.3% respectively (p<0.01 for both). Aggrenox decreased TIA by 35.9% compared to placebo (p<0.001).

Bleeding was more frequent and more often moderate or severe/fatal in both aspirin containing regimens. Bleeding rates were 8.2% (aspirin alone), 8.7% (Aspirin/Dipyridamole), 4.7% (Dipyridamole alone), 4.5% (placebo).
Summary
Aspirin 25 mg bid and dipyridamole ER 200 mg bid are equally effective for ischemic stroke and TIA prevention. Aggrenox (aspirin/dipyridamole) provides additional risk reduction compared to either agent alone. Low dose aspirin is still associated with a higher bleeding risk compared to dipyridamole.
Implications
None.
Related Figures
[7]