Review Articles
Low molecular weight heparin versus aspirin for acute ischemic stroke: A systematic review*

https://doi.org/10.1053/jscd.2002.126694Get rights and content

Abstract

Aspirin is the standard treatment for acute ischemic stroke, although heparins are widely prescribed. We performed a systematic review of randomized controlled trials to compare the safety and efficacy of low molecular weight heparins (LMWH) with aspirin in acute ischemic stroke. Two completed randomized controlled trials involving 1,933 patients were identified; 1 trial only included patients with presumed cardioembolic stroke. As compared with aspirin, treatment with heparin was associated with a significant reduction in symptomatic venous thromboembolism (odds ratio [OR] - 0.29, 95% confidence interval [CI] - 0.12-0.66) and an increase in major extracranial hemorrhage (OR - 2.57, 95% CI - 1.01-6.52). Nonsignificant increases in end-of-treatment case fatality (OR - 1.35, 95% CI - 0.87-2.08) and symptomatic intracranial haemorrhage (OR - 1.82, 95% CI - 0.68-4.87) were seen; symptomatic intracranial haemorrhage was significantly raised (OR - 4.26, 95% CI - 1.04-17.4) with heparin in patients treated within 24 hours of stroke onset. Stroke recurrence (OR - 1.24, 95% CI - 0.79-1.94) and deterioration (OR - 1.13, 95% CI - 0.85-1.50) during treatment and end-of-trial death (OR - 1.00, 95% CI - 0.77-1.30) or dependency and case fatality (OR - 1.03, 95% CI - 0.85-1.25) did not differ between the 2 treatments. No benefit of LMWH over aspirin was seen in patients with presumed cardioembolic stroke. Low molecular weight heparin should not replace aspirin in the routine management of patients with ischemic stroke, including those with presumed cardioembolic stroke. Copyright © 2002 by National Stroke Association

Section snippets

Study identification

Studies were identified through searches of the Cochrane Library (Version 3, 2001), MEDLINE, and EMBASE using the search terms: ((heparin-low-molecular-weight or certoparin or dalteparin or enoxaparin or nadroparin or reviparin or tinzaparin) and aspirin) and (stroke or cerebr*). Searches of published systematic reviews3, 8, 9, 10, 11 and other reviews12, 13, 14, 15 of anticoagulant treatment in acute stroke, the reference lists of existing reports of LMWH in acute stroke, and a study of

Study identification and characteristics

Two completed trials were identified which fulfilled the inclusion criteria (Table 1).Both studies, Heparin in Acute Embolic Stroke Trial (HAEST)18, 19 and Tinzaparin in Acute Ischaemic Stroke Trial,17 had been published as full papers; data for TAIST were obtained from the final statistical analysis file (P Soerensen, Statistician, Leo Pharmaceuticals). Abstracted data from each trial were checked with the first authors of the trial papers. The 2 trials together studied 1,933 patients who were

Discussion

The routine use of LMWH in acute ischemic stroke by many stroke physicians can be questioned by the results of this systematic review. As compared with aspirin, LMWH did not improve functional outcome, a finding which mirrors an earlier systematic review comparing LMWH with placebo/control.9 This failure might simply reflect that LMWH are ineffective or that any beneficial effects are offset by hazard (for example, severe intracranial or extracranial bleeding).

A number of mechanisms have been

Acknowledgements

Philip Bath is Stroke Association Professor of Stroke Medicine; Fiona Bath was funded by the UK National Health Service Executive (Trent), grant No SPGS 236. The study was presented, in part, at the 10th European Stroke Conference, Lisbon, May 2001.27 The study received no funding from the pharmaceutical industry. We thank Eivind Berge (HAEST) and Ewa Lindenstrøm and Per Sørensen (Leo Pharmaceuticals, TAIST) for providing data for the analyses. Philip Bath was principal investigator and

References (27)

  • M Cohen et al.

    A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease

    N Engl J Med

    (1997)
  • PMW Bath

    Low molecular weight heparin in acute stroke

    Expert Opin Investig Drugs

    (1998)
  • PMW Bath et al.

    Low molecular weight heparins and heparinoids in acute ischaemic stroke: A systematic review

    Stroke

    (2000)
  • Cited by (16)

    • Strokelore: Early Anticoagulation for Large Ischemic Strokes

      2021, Journal of Stroke and Cerebrovascular Diseases
    • Antithrombotic Therapy for Treatment of Acute Ischemic Stroke

      2015, Stroke: Pathophysiology, Diagnosis, and Management
    • Targeted use of heparin, heparinoids, or low-molecular-weight heparin to improve outcome after acute ischaemic stroke: An individual patient data meta-analysis of randomised controlled trials

      2013, The Lancet Neurology
      Citation Excerpt :

      Although heparins (unfractionated heparin, low-molecular-weight heparin, and heparinoids) can reduce the risk of recurrent ischaemic stroke, deep vein thrombosis, and pulmonary embolism, they also increase the risk of symptomatic intracranial and extracranial haemorrhage.5 In stroke, the benefits are exactly offset by the harms, and hence in systematic reviews of grouped data from randomised controlled trials of subcutaneous heparins, there was no net observable effect of anticoagulants on death or disability measured several months after stroke (even in selected subtypes).6–8 However, some clinicians still use heparin or low-molecular-weight heparin to prevent early recurrent stroke in patients who are felt to be at particularly high risk.9–13

    • Consensus on acute ischemic stroke

      2019, Medicina (Argentina)
    View all citing articles on Scopus
    *

    Address reprint requests to Philip Bath, FRCP, Division of Stroke Medicine, University of Nottingham, City Hospital Campus, Nottingham NG5 1PB, UK.

    View full text