Low-Molecular-Weight Heparin and Early Neurologic Deterioration in Acute Stroke Caused by Large Artery Occlusive Disease

Study Questions:

What are the risks and benefits associated with the use of low molecular weight heparin (LMWH) in early ischemic stroke patients?


The authors reported data from FISS-tris (the Fraxiparin In Stroke Study For The Treatment Of Ischemic Stroke), a prospective, multicenter, randomized clinical trial comparing LMWH with aspirin for early treatment of patients with acute ischemic stroke caused by large artery occlusive disease. Subjects diagnosed with ischemic stroke within 48 hours of onset, and found to have symptomatic large artery occlusive disease, were randomized to 3,800 antifactor Xa IU/0.4 ml LMWH subcutaneously twice daily or 160 mg aspirin once daily for 10 days, after which all subjects received aspirin 80-300 mg daily for 6 months. The primary outcome of interest was prevention of early neurologic deterioration, defined as a composite endpoint of progressive stroke, early return to ischemic stroke, and symptomatic intracranial hemorrhage.


Among 603 patients recruited, 353 were included in the study. The composite endpoint occurred within the first 10 days in 6.7% (12/180) of LMWH patients, compared with 13.9% (24/173) in aspirin-treated patients. LMWH was associated with significant risk reduction for the composite endpoint (adjusted risk ratio, 7.2%; odds ratio [OR], 0.44; 95% confidence interval [CI], 0.21-0.92). There was a significant reduction in stroke progression associated with LMWH use (5.0% vs. 12.7%; OR, 0.36; 95% CI, 0.16-0.81). There was a nonsignificant difference in early recurrent ischemic stroke (1.1% vs. 0%), as well as symptomatic intracranial hemorrhage (0.6% vs. 1.2%), and cerebral hemorrhage (2.2% vs. 2.9%), for LMWH versus aspirin, respectively. Early neurologic deterioration was significantly associated with 6-month disability, regardless of treatment modality used.


The authors concluded that for patients with acute ischemic stroke due to large artery occlusive disease, treatment with LMWH within 48 hours of stroke may reduce early neurologic deterioration in the first 10 days, mainly by preventing stroke progression. The authors further opined that the similar rate of intracranial cerebral hemorrhage between LMWH and aspirin suggests that LMWH may be safely used in acute ischemic stroke.


In the setting of ischemic stroke, there is the constant challenge of balancing prevention of further thrombotic or thromboembolic complications, with the possibility of provoking intracranial hemorrhage, when contemplating the use of further anticoagulant or antithrombotic therapy. This randomized study suggests that early neurologic deterioration may be decreased by the use of LMWH versus aspirin acutely. The study design administered LMWH for only the first 10 days after acute stroke. For the management of acute stroke patients, these data need to be considered in the context of other trials, but suggest no harm and possible benefit to early short-term use of LMWH versus aspirin in the setting of acute ischemic stroke associated with extracranial arterial disease. For the non-neurologist, these data provide reassurance that the use of LMWH for the purpose of venous thromboembolism prophylaxis is certainly safe, even in the setting of acute ischemic stroke.

Clinical Topics: Anticoagulation Management, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism

Keywords: Odds Ratio, Stroke, Heparin, Low-Molecular-Weight, Venous Thromboembolism, Intracranial Hemorrhages, Cardiovascular Diseases, Nadroparin, Confidence Intervals, Risk Assessment, Cerebral Arterial Diseases

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