Correspondence

Low-Molecular-Weight Heparin for the Treatment of Acute Ischemic Stroke

N Engl J Med 1996; 334:1407May 23, 1996

Article

To the Editor:

The conclusion by Kay et al. (Dec. 14 issue)1 that low-molecular-weight heparin improves the outcomes of patients with acute ischemic stroke can be questioned for two reasons. First, aspirin should have been administered to the patients in the control group, because aspirin is regarded as standard therapy in this clinical situation.2 Without the administration of aspirin in the control group, it cannot be concluded that nadroparin had a significant effect beyond the current standard of care.

Second, there was a high rate of complications in the placebo group after the treatment period, including an increased number of patients with hemorrhagic transformation (almost twice the number among those who received anticoagulation therapy), and an increased number of recurrent ischemic strokes (more than double the number in the high-dose group). The authors “speculate that antithrombotic treatment [with nadroparin] may have reduced the volume of the infarct by limiting the extension of thrombus to the ischemic penumbra . . . and by maintaining blood flow in that region. Treated patients would thus have more potential for survival and recovery.” Aspirin likewise might have adequately limited the extension of infarction in the placebo group.

We may lack strong data supporting the efficacy of aspirin or heparin for the treatment of acute ischemic stroke, but when there are no contraindications, aspirin is well established as the standard treatment in acute nonhemorrhagic ischemic stroke.

Jeffrey M. Bloom, M.D.
San Luis Medical Clinic, San Luis Obispo, CA 93401

2 References

1. 1

   Kay R, Wong KS, Yu YL, et al. Low-molecular-weight heparin for the treatment of acute ischemic stroke. N Engl J Med 1995;333:1588-1593
   Full Text | Web of Science | Medline

2. 2

   Barnett HJM, Eliasziw M, Meldrum HE. Drugs and surgery in the prevention of ischemic stroke. N Engl J Med 1995;332:238-248
   Full Text | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: The value of aspirin, if any, in the treatment of acute ischemic stroke has not been established.1,2 The recommendations by Barnett et al. refer to the prevention of ischemic stroke.3 For the use of aspirin in patients with acute ischemic stroke, the only support from randomized studies comes from a recently suspended clinical trial comparing streptokinase, aspirin, and the two drugs combined.4 In that trial, aspirin reduced the risk of death or severe disability at six months by 10 percent, but this reduction was not statistically significant. At least two major clinical trials (the International Stroke Trial and the Chinese Acute Stroke Trial) are currently investigating the effect of aspirin given within 48 hours after an ischemic stroke. If these trials show that aspirin improves the outcome, then it will be reasonable to discuss whether future trials of therapy for acute stroke should include the administration of aspirin in the control group.

The higher rates of complications in the placebo group in our study were not statistically significant. In the case of hemorrhagic transformation of the infarct, there were more hematomas in the low-dose group than in either the high-dose group or the placebo group (Table 1Table 1Findings on Second Computed Tomographic Scans in 245 Patients, According to Treatment Group.). The numbers were small, and such differences could well have been due to chance.

Richard Kay, M.D.
Ka Sing Wong, M.B.
Jean Woo, M.D.
Chinese University of Hong Kong, Shatin, Hong Kong

4 References

1. 1

   Sandercock PA, van den Belt AG, Lindley RI, Slattery J. Antithrombotic therapy in acute ischaemic stroke: an overview of the completed randomised trials. J Neurol Neurosurg Psychiatry 1993;56:17-25
   CrossRef | Web of Science | Medline

2. 2

   Adams HP Jr, Brott TG, Crowell RM, et al. Guidelines for the management of patients with acute ischemic stroke: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 1994;25:1901-1914
   CrossRef | Web of Science | Medline

3. 3

   Barnett HJM, Eliasziw M, Meldrum HE. Drugs and surgery in the prevention of ischemic stroke. N Engl J Med 1995;332:238-248
   Full Text | Web of Science | Medline

4. 4

   Multicentre Acute Stroke Trial-Italy (MAST-I) Group. Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Lancet 1995;346:1509-1514
   Web of Science | Medline