Design of ESPRIT: An International Randomized Trial for Secondary Prevention after Non-Disabling Cerebral Ischaemia of Arterial Origin

Abstract

The ESPRIT trial addresses the problem that aspirin, the standard therapy for secondary prevention of vascular complications after a transient ischaemic attack (TIA) or ischaemic stroke of arterial origin, reduces the risk of serious vascular events by only about 13%. Anticoagulants may be an alternative, as these have proved highly efficacious in trials after myocardial infarction and after cerebral ischaemia with atrial fibrillation. After cerebral ischaemia of presumed arterial origin, high-intensity anticoagulation (INR 3.0–4.5) is not safe, but the value of anticoagulation with an INR between 2.0 and 3.0 is still unknown. Secondly, a recent, large trial showed that the combination of aspirin and dipyridamole prevents more major vascular events than aspirin alone, but several earlier trials did not find such an advantage. In ESPRIT, patients with a TIA or minor ischaemic stroke (Rankin grade ≤3) will be randomized between oral anticoagulation (INR 2.0–3.0), the combination of dipyridamole (400 mg daily) plus aspirin (in any dose between 30 and 325 mg daily) and aspirin only. Primary outcome is the composite event ‘death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction or major bleeding complication’, whichever occurs first. Outcome assessment will be blinded. The recruitment of a total of 4,500 patients from more than 10 countries is planned; the mean follow-up will be 3 years.

The Prognostic Effects of Poststroke Cognitive Impairment No Dementia and Domain-Specific Cognitive Impairments in Nondisabled Ischemic Stroke Patients

“…Detailed methodology for the main study has been previously reported. 10 Briefly, patients were eligible if they were within 6 months of a transient ischemic attack (including transient monocular blindness) or a nondisabling ischemic stroke (grade Յ3 on the modified Rankin scale 11 [mRS]) of presumed arterial origin. The exclusion criteria were: a possible cardiac source of embolism, high-grade carotid stenosis for which carotid endarterectomy or endovascular treatment was planned, moderate to severe leukoaraiosis on brain imaging (for randomization into anticoagulation), any blood coagulation disorder, any contraindication for aspirin or dipyridamole, and a limited life expectancy.…”

Dipyridamole for Preventing Recurrent Ischemic Stroke and Other Vascular Events

“…Recently, dipyridamole was reported to have no effect on BP (at Ͼ1 year) in an interim analysis involving data from 591 patients in the ongoing European/Australian Stroke Prevention in Reversible Ischemia Trial (ESPRIT) trial. 20,28 The small size and possible presence of terminal digit preference mean that this may be a false neutral finding. 28 Alternatively, the effect of dipyridamole on BP may be temporary.…”

Secondary stroke prevention: Review of clinical trials

“…71 Finally, in the largest prospective stroke prevention study yet, PRoFESS (described briefly above in reference to telmisartan) will evaluate the efficacy of two dual antiplatelet regimens: aspirin plus extended-release dipyridamole versus aspirin plus clopidogrel. 63 …”