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.

Keywords:
Stroke, ischaemic, Secondary prevention, Trial
1.
Antiplatelet Trialists’ Collaboration: Collaborative overview of randomised trials of antiplatelet therapy. I. Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ 1994;308:81–106.
2.
Algra A, van Gijn J: Aspirin at any dose above 30 mg offers only modest protection after cerebral ischaemia. J Neurol Neurosurg Psychiatry 1996;60:197–199.
3.
Algra A, van Gijn J: Cumulative meta-analysis of aspirin efficacy after cerebral ischaemia of arterial origin (letter). J Neurol Neurosurg Psychiatry 1999;66:255.
4.
CAPRIE Steering Committee: A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329–1339.
5.
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.
6.
The ESPS-2 Group: European Stroke Prevention Study 2: Efficacy and safety data. J Neurol Sci 1997;151(suppl):S1–77.
7.
Guiraud-Chaumeil B, Rascol A, David J, Boneu B, Clanet M, Bierme R: Prévention des récidives des accidents vasculaires cérébraux ischémiques par les anti-agrégants plaquettaires: Résultats d’un essai thérapeutique controlé de 3 ans. Rev Neurol (Paris) 1982;138:367–385.
8.
Bousser MG, Eschwege E, Haguenau M, et al: ‘AICLA’ controlled trial of aspirin and dipyridamole in the secondary prevention of athero-thrombotic cerebral ischemia. Stroke 1983;14:5–14.
9.
American-Canadian Co-operative Study Group: Persantine Aspirin Trial in cerebral ischemia. Part II: Endpoint results. Stroke 1985;16:406–415.
10.
Kaye J: A Trial to Evaluate the Relative Roles of Dipyridamole and Aspirin in the Prevention of Deep Vein Thrombosis in Stroke Patients. Internal report. Bracknell, Boehringer Ingelheim, 1990.
11.
Smith P, Arnesen H, Holme I: The effect of warfarin on mortality and reinfarction after myocardial infarction. N Engl J Med 1990;323:147–152.
12.
The Sixty Plus Reinfarction Study Research Group: A double-blind trial to assess long-term oral anticoagulant therapy in elderly patients after myocardial infarction. Lancet 1980;ii:989–994.
13.
Anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis (ASPECT) Research Group: Effect of long-term oral anticoagulant treatment on mortality and cardiovascular morbidity after myocardial infarction. Lancet 1994;343:499–503.
14.
The EPSIM Research Group: A controlled comparison of aspirin and oral anticoagulants in prevention of death after myocardial infarction. N Engl J Med 1982;307:701–708.
15.
EAFT (European Atrial Fibrillation Trial) Study Group: Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. Lancet 1993;342:1255–1262.
16.
Stroke Prevention in Atrial Fibrillation Investigators: Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial. Lancet 1996;348:633–638.
17.
Coumadin Aspirin Reinfarction Study (CARS) Investigators: Randomised double-blind trial of fixed low-dose warfarin with aspirin after myocardial infarction. Lancet 1997;350:389–396.
18.
The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) Study Group: A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin. Ann Neurol 1997;42:857–865.
19.
Mohr JP, WARSS Group: Design considerations for the Warfarin-Antiplatelet Recurrent Stroke Study. Cerebrovasc Dis 1995;5:156–157.
20.
Hylek EM, Skates SJ, Sheehan MA, Singer DE: An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation. N Engl J Med 1996;335:540–546.
21.
van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J: Interobserver agreement for the assessment of handicap in stroke patients. Stroke 1988;19:604–607.
22.
Bamford JM, Sandercock PAG, Warlow CP, Slattery J: Interobserver agreement for the assessment of handicap in stroke patients (letter). Stroke 1989;20:828.
23.
van Swieten JC, Hijdra A, Koudstaal PJ, van Gijn J: Grading white matter lesions on CT and MRI: A simple scale. J Neurol Neurosurg Psychiatry 1990;53:1080–1083.
24.
Algra A, van Gijn J: Science unblinded (letter, comment). Lancet 1994;343:1040.
25.
Koudstaal PJ, van Gijn J, Loeliger EA, et al: Transient ischemic attacks with and without a relevant infarct on computed tomographic scans cannot be distinguished clinically. Arch Neurol 1991;48:916–920.
26.
Loeliger EA, Lewis SM: Progress in laboratory control of oral anticoagulants. Lancet 1982;ii:318–320.
27.
Rosendaal FR, Cannegieter SC, van der Meer FJ, Briet E: A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993;69:236–239.
28.
Self SG, Mauritsen RH, Ohara J: Power calculations for likelihood ratio tests in generalized linear models. Biometrics 1992;48:31–39.
29.
The Dutch TIA Trial Study Group: A comparison of two doses of aspirin (30 mg vs. 283 mg a day) in patients after a transient ischemic attack or minor ischemic stroke. N Engl J Med 1991;325:1261–1266.
30.
Cox DR: Regression models and life-tables. J R Stat Soc (B) 1972;34:187–202.
31.
O’Brien PC, Fleming TR: A multiple testing procedure for clinical trials. Biometrics 1979;35:549–556.
© 2000 S. Karger AG, Basel
2000
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.