The European Stroke Prevention Study (ESPS)

Article: The European Stroke Prevention Study (ESPS), The Lancet, Volume 330, Issue 8572, 1351 - 1354

Question:

Among patients with a clinical diagnosis of cerebrovascular event of atherothrombotic origin (transient ischemic attack, reversible ischemic neurological deficit, or stroke), does the use of dipyridamole (DP) in combination with aspirin (ASA) prevent a first stroke or death following an initial qualifying cerebral event (ie, TIA or RIND), or second stroke or death following an initial stroke?

Answer:

Compared to placebo, taking a combination of dipyridamole and aspirin within 3 months of a TIA, RIND or ischemic stroke, significantly reduced the incidence of stroke or death.

Design:

  • Multicenter, double-blind, prospective, randomized

  • N= 2500

  • Setting: 16 centers in 6 European countries (Belgium, Denmark, Finland, Holland, Ireland, UK)

  • Follow-up: 24 months

  • Recruitment: 1979-1984

  • Analysis: Intention to treat and explanatory

Intervention:

  • Arm 1: Dipyridamole 75mg TID + Aspirin 325mg TID (n=1250) - given in 1 combined pill

  • Arm 2: Placebo TID (n=1250)

Inclusion Criteria:

  • Male or female of any age or race

  • Cerebrovascular event (transient ischemic attack, reversible ischemic neurological deficit, or stroke) less than 3 months before initiation of drug

    • Transient Ischemic Attack (TIA) is an event after which neurological deficit recovers within 24h

    • Reversible ischemic neurological deficit (RIND) is an event after which the deficit lasts longer than 24h, but recovers within seven days (minor stroke)

    • Stroke as an event after which the deficit persists for longer than seven days

Exclusion Criteria:

  • Poorly controlled hypertension (diastolic pressure consistently >110mg Hg)

  • Uremia (blood urea >12mmol/l)

  • Inadequately controlled diabetes

  • Known peptic ulceration in the past two years

  • Bleeding diasthesis

  • Previous antiplatelet or anticoagulant treatment

  • Vascular surgery for, or relevant to, the qualifying event

Patient Population:

  • Baseline characteristics not reported

Endpoints:

  • Primary:

    • Stroke within the 24mo follow-up

    • Death from any cause within the 24mo follow-up

Results:

  • Stroke or death from any cause occurred in 473 patients (190 in DP-ASA group, 283 in placebo group, p<0.001)

  • Stroke occurred in 298 patients (114 in DP-ASA group, 184 in placebo group, p<0.001)

  • Death occurred in 264 patients (108 in DP-ASA group, 156 in placebo group, p<0.01)

Notes:

  • 639 patients (26%) of the 2500 patients were excluded after being found ineligible for entry because of breaches of the inclusion criteria or misdiagnosis. 1861 fully met the entry criteria.

  • The treatment and placebo groups were reportedly well matched for sex, age, initial diagnosis, BP and smoking habits

  • 1298 patients completed the 24mo follow-up while 800 dropped out for varying reasons (side-effects, carotid endarterectomy, other non-medical factors, etc)

Current Guidelines:

  • Administration of aspirin is recommended in patients with acute ischemic stroke (AIS) within 24 to 48 hours after onset. For those treated with IV alteplase, aspirin administration is generally delayed until 24 hours later but might be considered in the presence of concomitant conditions for which such treatment given in the absence of IV alteplase is known to provide a substantial benefit or withholding such treatment is known to cause substantial risk

  • Aspirin is not recommended as a substitute for acute stroke treatment in patients who are otherwise eligible for IV alteplase or mechanical thrombectomy.

  • The efficacy of IV tirofiban and eptifibatide is not well established. Further clinical trials are needed.

  • The administration of another glycoprotein IIb/IIIa receptor antagonists, including abciximab, in the treatment of AIS is potentially harmful and should not be performed. Further research testing the safety and efficacy of these medications in patients with AIS is required

  • In patients presenting with minor stroke, treatment for 21 days with dual antiplatelet therapy (aspirin and clopidogrel) begun within 24 hours can be beneficial for early secondary stroke prevention for a period of up to 90 days from symptom onset

  • Ticagrelor is not recommended (over aspirin) in the acute treatment of patients with minor stroke