(Stroke. 1999;30:2238-2248.)
© 1999 American Heart Association, Inc.
Letters to the Editor |
Antiplatelet Therapy in Acute Cerebral Ischaemia
Department of Clinical Neurosciences, Western General Hospital, Edinburgh, UK
Clinical Trial Service Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
 |
Introduction |
|---|
 Top Introduction ReferencesIntroduction References |
|---|
To the Editor:
The review by Bednar and Gross1 of antiplatelet therapy in acute cerebral ischemia mistakenly suggested that "only 1 study, the Multicentre Acute Stroke Trial–Italy (MAST-I), entered patients within 6 hours of the ictus." The International Stroke Trial (IST) and the Chinese Acute Stroke Trial (CAST) randomized a total of 5629 patients within the first 6 hours,2 3 finding good evidence of benefit.2 3 4 Thus, antiplatelet therapy has already been evaluated in the acute phase of cerebral ischemia, and indeed, the number of patients randomized in aspirin trials within 6 hours is approximately the same as those randomized in all the trials of thrombolytic therapy for acute ischemic stroke.5 We disagree with Bednar and Gross that "larger studies are needed to confirm these findings."
|
References |
|---|
|
TopIntroductionReferencesIntroduction References |
|---|
-
Bednar MM, Gross CE. Antiplatelet
therapy in acute cerebral ischemia. Stroke.. 1999;30:887–893.
[Abstract/Free Full Text] - International Stroke Trial Collaborative Group (IST). A randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. Lancet.. 1997;349:1569–1581.[Medline] [Order article via Infotrieve]
- Chinese Acute Stroke Trial Collaborative Group (CAST). Randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. Lancet.. 1997;349:1641–1649.[Medline] [Order article via Infotrieve]
- Chen ZM, Sandercock P, on behalf of the AntiThrombotic Trialists Collaboration (ATT). Indications for early aspirin use in acute stroke: a systematic overview of over 40,000 randomised patients. Cerebrovasc Dis. 1998;8(suppl 4):38. Abstract.
- Wardlaw J, del Zoppo G. Thrombolysis for acute ischaemic stroke (Cochrane review). In: The Cochrane Library. Oxford, UK: Update Software; 1999; issue 2.
Response
Division of Neurosurgery, University of Vermont, Burlington, Vermont
Key Words: aspirin • stroke, acute • clinical trials
|
Introduction |
|---|
|
TopIntroductionReferencesIntroduction References |
|---|
We appreciate the interest by Drs Sandercock, Warlow, Dennis, and Chen in our review.1 In this review, we have correctly stated that there were "two large-scale, randomized, prospective clinical trials, the International Stroke Trial (IST)2 and the Chinese Acute Stroke Trial (CAST)3 ... in which aspirin ... was administered within 48 hours of the ischemic event." Our review also correctly stated that MAST-Italy4 is the only randomized clinical study to administer aspirin within 6 hours of the ictus. These statements certainly do not exclude the fact that a small subset of patients from IST and CAST were entered from hours 0 to 6.
We find it very surprising that Dr Sandercock and coauthors would categorically state that the combined randomization of 5629 patients to aspirin or placebo from hours 0 to 6 in the IST and CAST trials demonstrates "good evidence of benefit." In fact, there is absolutely no statistical support for this contention. Moreover, when one analyzes patients from both IST and CAST who received aspirin in the acute period (0 to 3 hours), the results are very different: one finds that patients receiving aspirin in the IST trial derived absolutely no benefit from aspirin, whereas this subpopulation of patients received the greatest benefit in the CAST trial!
Drs Sandercock, Warlow, Dennis, and Chen further note that they "disagree ... that larger studies are needed to confirm" the benefit of aspirin within 6 hours of stroke. We strongly disagree. Indeed, their statement appears to be completely contradictory to the statement by Dr Sandercock in the IST study. In that study, Dr Sandercock and coauthors noted that "the combination of low-dose subcutaneous heparin plus aspirin looked as if it might be better in the short term than aspirin alone. However, these analyses were based on a relatively small number of patients (6,000) and ... this hypothesis needs to be tested by a further trial."2
Thus, although combination aspirin plus low-dose heparin showed even greater early benefit and randomized even more patients than seen for acute (0 to 6 hours) aspirin therapy, Drs Sandercock, Warlow, Dennis, and Chen disagree that there is a need for larger studies to confirm the findings seen with aspirin, yet contend that the "small number" of patients studied with low-dose heparin warrants a further trial!
It would appear that there is a lack of consistency in the application of study design and robust statistical analysis by Drs Sandercock and coauthors. It is our hope that future studies will continue to study the role of aspirin as a potential strategy for both acute (0 to 6 hours) and delayed stroke therapy to more clearly define the benefit.
|
References |
|---|
|
TopIntroductionReferencesIntroduction References |
|---|
- Bednar MM, Gross CE. Antiplatelet therapy in acute cerebral ischemia. Stroke.. 1999;30:887–893.
- International Stroke Trial Collaborative Group (IST). A randomized trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. Lancet.. 1997;349:1569–1581.
- Chinese Acute Stroke Trial Collaborative Group (CAST). Randomized placebo-controlled trial of early aspirin use in 20,000 patients with acute ischemic stroke. Lancet.. 1997;349:1641–1649.
- Multicentre Acute Stroke Trial–Italy Group (MAST-I): Randomized controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke [see comment]. Lancet.. 1995;346:1509–1514.[Medline] [Order article via Infotrieve]
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||