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(Stroke. 2005;36:933.)
© 2005 American Heart Association, Inc.

Letters to the Editor

Oral Anticoagulation in Secondary Prevention After Cerebral Ischemia of Arterial Origin

P.H.A. Halkes, MD for the ESPRIT Study Group

Department of Neurology, University Medical Center Utrecht, Utrecht, the Netherlands

Letter to the Editor:

We react to the article by Amarenco and Donnan¹ in which they discuss stroke prevention strategies after publication of the MATCH trial. In our opinion, they rush to conclusions about the value of oral anticoagulants in the secondary prevention after noncardioembolic stroke.

SPIRIT² did not show that oral anticoagulants were inferior to aspirin in terms of efficacy and net benefit to prevent stroke and death in patients with a noncardioembolic stroke, as stated by the authors. SPIRIT was designed to compare the efficacy and benefit of oral anticoagulants with those of aspirin, but the trial was stopped early because of an excessively high incidence of major bleeding complications in the anticoagulation group. The only conclusion that can be drawn from this trial is that oral anticoagulants with an aimed INR of 3.0 to 4.5 are not as safe as aspirin in patients with a noncardioembolic stroke. The limited number of patients in the trial and the short follow-up do not allow conclusions on the efficacy in preventing stroke; the 95% confidence interval for ischemic events ranged from a 40% benefit for anticoagulants to a 43% benefit for aspirin. From SPIRIT and WARSS,³ together it may be inferred that anticoagulation is not the therapy of choice if its target INR is either high (SPIRIT: 3.0 to 4.5, average 3.3) or low (WARSS: 1.4 to 2.8, average 2.0). However, this leaves an intermediate target (2.0 to 3.0) for which no efficacy data in the prevention of stroke are known. Observational data suggest that this intermediate target is the optimum in the benefit–risk balance of oral anticoagulation for patients with noncardioembolic stroke.⁴

The European/Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT)⁵ aims to fill this gap by comparing oral anticoagulants with an aimed INR of 2.0 to 3.0 with aspirin in the secondary prevention after noncardioembolic stroke. Only after completion of this trial can definite conclusions on the efficacy of oral anticoagulants be drawn.

References

1. Amarenco P, Donnan GA. Should the MATCH results be extrapolated to all stroke patients and affect ongoing trials evaluating clopidogrel plus aspirin? Stroke. 2004; 35: 2606–2608.[Free Full Text]
2. A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin. The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) Study Group. Ann Neurol. 1997; 42: 857–865.[CrossRef][Medline] [Order article via Infotrieve]
3. Mohr JP, Thompson JL, Lazar RM, Levin B, Sacco RL, Furie KL, Kistler JP, Albers GW, Pettigrew LC, Adams HP Jr, Jackson CM, Pullicino P. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med. 2001; 345: 1444–1451.[Abstract/Free Full Text]
4. Torn M, Algra A, Rosendaal FR. Oral anticoagulation for cerebral ischemia of arterial origin: high initial bleeding risk. Neurology. 2001; 57: 1993–1999.[Abstract/Free Full Text]
5. De Schryver EL. Design of ESPRIT: an international randomized trial for secondary prevention after non-disabling cerebral ischaemia of arterial origin. European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) group. Cerebrovasc Dis. 2000; 10: 147–150.[CrossRef][Medline] [Order article via Infotrieve]

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