ESPRIT (European/Australasian Stroke Prevention in Reversible Ischaemia Trial) and related studies

Abstract

1. We compared 120 patients who had had a large subcortical infarct with 324 who had had a small deep infarct and with 211 who had had a cortical infarct from the same cohort. We found no differences in risk factor profiles between the three groups, nor a difference in stroke recurrence rate. 2. We demonstrated, by means of a questionnaire filled in by 29 neurologists with special interest in stroke, that there is very little agreement on the classification of cause of death in patients who die after a stroke in the setting of a clinical trial. We developed guidelines for the classification of the cause of death after stroke, with the criteria ‘interval between stroke and death’ (cutoff point at 1 month) and ‘best Rankin grade after stroke’ (cutoff at 3). 3. The results of the first part of the European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) are described, in which patients who suffered a Transient Ischaemic Attack (TIA) or non disabling ischaemic stroke of presumed arterial origin were randomized between the combination therapy of aspirin plus dipyridamole (n=1363) and aspirin alone (n=1376). Less patients assigned to the combination therapy (173, 13%) than to aspirin alone (216, 16%) suffered the primary outcome event, which was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever happened first. The corresponding hazard ratio was 0.80 (95% confidence interval 0.66-0.98). 4. The results of the second, prematurely halted, part of ESPRIT are presented. In this part a comparison was made between medium intensity oral anticoagulants (aimed international normalized ratio (INR) 2.0-3.0) and aspirin in the secondary prevention after TIA or non disabling ischaemic stroke of arterial origin. There was no difference in the incidence of the primary outcome event (99 of 536 patients, 19% versus 98 of 532, 18%). There were, however, more major bleeding complications in patients assigned to anticoagulation (45 vs. 18, hazard ratio 2.56 (95% confidence interval 1.48-4.43). 5. The results of an individual patient data based meta-analysis of all trials that compared the combination therapy of aspirin plus dipyridamole with aspirin alone in the secondary prevention after TIA or stroke of arterial origin are presented. Data from 7612 patients (3800 allocated to aspirin plus dipyridamole and 3812 to aspirin alone) were available for this analysis. The hazard ratio for the composite event of vascular death, non-fatal myocardial infarction and non-fatal stroke was 0.82 (95% CI 0.72-0.92). Hazard ratios did not differ in subgroup analyses based on patient characteristics, nor across baseline risk strata as assessed with two different risk scores. 6. We did an exploratory analysis on data from ESPRIT and from the Second European Stroke Prevention Study (ESPS 2), with the aim to identify risk factors for the development of headache during treatment with dipyridamole. The factors we found to be associated with discontinuation of dipyridamole because of headache were female sex, no (relevant) ischemic lesion on brain imaging and not smoking.