European Stroke Prevention Study 2 - ESPS-2


The goal of the trial was to evaluate treatment with dipyridamole, aspirin, the combination of the two, or placebo for the secondary prevention of recurrent ischemic stroke.

Study Design

Study Design:

Patients Enrolled: 6602
Mean Follow Up: 2 years
Mean Patient Age: Mean age 66.7 years
Female: 42

Patient Populations:

Prior stroke or transient ischemic attack (TIA) in the prior three months


Recent history of peptic ulcer or other gastrointestinal bleeding, hypersensitivity or intolerance to study medication, bleeding disturbances, any condition requiring continued use of aspirin or anticoagulants, or any life-threatening condition

Primary Endpoints:

Stroke; death; and composite of stroke or death

Secondary Endpoints:

TIA; myocardial infarction; ischemic events; other vascular events

Drug/Procedures Used:

Patients were randomized in a double-blind manner to aspirin alone (50 mg daily) (n=1649), modified-release dipyridamole alone (400 mg daily) (n=1654), the two agents in a combined formulation (n=1650), or placebo (n=1649).

Principal Findings:

The majority of patients in the trial had a prior ischemic stroke (76.3%); 23.7% had a TIA. Hypertension was present in 60.5% of patients, ischemic heart disease in 35.1%, and diabetes in 15.3%.

Through 2 years, stroke occurred in 12.9% of the aspirin group, 13.2% of the dipyridamole group, 9.9% of the combination group, and 15.8% of the placebo group (4-way p<0.001; p<0.01 for combination therapy vs each other group). There was no difference between the groups in mortality (10.9% for aspirin alone, 11.4% for dipyridamole alone, 11.2% for combination, 12.3% for placebo; 4-way p=0.616), but the composite of death or recurrent stroke did differ (19.9%, 19.4%, 17.4%, 23.0%, respectively; 4-way p<0.001; p<0.05 for each group vs placebo). TIA occurred in 12.6% of the aspirin group, 13.2% of the dipyridamole alone, 10.6% of the combination group, and 16.5% of the placebo group (4-way p<0.001).

Adverse events occurred more frequently in the active treatment groups compared with placebo (n=990 for aspirin alone, n=1034 for dipyridamole alone, n=1056 for combination, n=933 for placebo). Bleeding occurred more frequently in the aspirin arms (8.2% for aspirin alone, 8.7% for combination) compared with the non-aspirin arms (4.7% for dipyridamole alone, 4.5% for placebo).


Among patients with prior stroke or TIA, combination treatment with aspirin and dipyridamole was associated with greater reductions in the composite of death or stroke at 2 years compared with aspirin alone, dipyridamole alone, or placebo. Both aspirin alone and dipyridamole alone were associated with reductions in death or stroke compared with placebo. Despite the relatively low dose of aspirin used in the trial, bleeding rates were higher in both aspirin arms.


Diener HC, Cunha L, Forbes C, Sivenius J, Smets P, Lowenthal A. European Stroke Prevention Study, 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996;143:1-13.

Clinical Topics: Prevention, Vascular Medicine, Statins, Hypertension

Keywords: Drug Combinations, Stroke, Myocardial Ischemia, Ischemic Attack, Transient, Platelet Aggregation Inhibitors, Secondary Prevention, Cerebrovascular Disorders, Hypertension, Dipyridamole, Hemorrhage, Diabetes Mellitus

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