European Stroke Prevention Study 2

The 1996 European Stroke Prevention Study 2 (ESPS-2) was a landmark, randomized, placebo-controlled clinical trial evaluating secondary prevention of ischemic stroke and transient ischemic attack (TIA) in 6,602 patients. It established that combining low-dose aspirin and extended-release dipyridamole provides an additive, superior reduction in stroke risk compared to either drug alone. (1)

This randomised placebo-controlled trial demonstrated that the combination of dipyridamole M/R and aspirin had a small but significant added benefit over either dipyridamole M/R or aspirin alone in the secondary prevention of stroke with only a slight increase in adverse effects:

• strokes with combination 9.5% versus aspirin 12.5%; P<0.001; NNT = 34
• however there was no statistically significant reduction in death from all causes, and the combined endpoint of stroke and/or death was no quite significant (P=0.056) with the combination compared with aspirin.

Comparing dipyridamole M/R to aspirin alone there was no significant difference between therapies.

Adverse effects - bleeding episodes were significantly more serious and frequent in the aspirin containing groups.

Note - for secondary stroke prevention NICE now recommends clopidogrel monotherapy first-line, with aspirin + dipyridamole only where clopidogrel is unsuitable.(2)

Reference:

1. Diener et al. European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996 Nov;143(1-2):1-13.
2. NICE. Stroke and transient ischaemic attack in over 16s: diagnosis and initial management. NICE guideline NG128. Published May 2019, last updated April 2022