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Am Fam Physician. 2007;76(12):1859-1864

Background: More than 700,000 strokes occur in American adults every year, and 88 percent of those strokes are ischemic. Venous thromboembolism is a common and serious complication of ischemic stroke and is a major cause of mortality, morbidity, and increased health care costs. Unless prophylaxis is provided, up to 75 percent of these patients may develop deep venous thrombosis (DVT) after hemiplegic stroke, and 20 percent may develop pulmonary embolism. Although clinical guidelines recommend prophylaxis following an acute ischemic stroke, the most effective regimen remains controversial. Physicians must balance the risk reduction of DVT, pulmonary embolism, and other related conditions with the dangers of hemorrhage. Sherman and colleagues designed this study to compare the safety and effectiveness of enoxaparin (Lovenox) versus unfractionated heparin.

The Study: There were 1,762 randomized patients treated for acute ischemic stroke at 200 centers in 15 countries. Patients were included if their symptoms were consistent with acute stroke; if they had motor impairment of the legs and were unable to walk on their own; if they had a score of 2 or more on the National Institutes of Health Stroke Scale; and if pathology was confirmed by computed tomography (CT) or magnetic resonance imaging. The study had an extensive list of exclusions, such as serious comorbidities, intracranial conditions, and contraindications to study materials. After stratification for stroke severity, participants were randomly assigned to treatment with 40 mg of enoxaparin subcutaneously daily or 5,000 U unfractionated heparin subcutaneously every 12 hours. Treatment began within 48 hours of the onset of symptoms and continued for 10 days.

The primary outcome was confirmed venous thromboembolism (i.e., DVT or pulmonary embolism) within 14 days. Venography or ultrasonography was performed to confirm DVT, and ventilation perfusion, thoracic helical CT, or pulmonary angiography was performed if pulmonary embolism was suspected. Secondary outcomes included symptomatic venous thromboembolism at 30, 60, and 90 days from randomization, and adverse events such as minor extracranial hemorrhage and thrombocytopenia.

Results: The 877 patients who were treated with enoxaparin were comparable with the 872 patients who were treated with unfractionated heparin in all significant demographic and clinical variables. In both groups, more than one half were men, 60 percent were white, and the average age was 66 years. About 70 percent of the participants had hypertension, 30 percent had diabetes, and 28 percent had a previous stroke. Study treatment was initiated an average of 1.2 days from onset of symptoms, and it continued for approximately 10.5 days in both groups.

At day 14, the frequency of venous thromboembolism was significantly reduced in patients who were treated with enoxaparin compared with unfractionated heparin (10 and 18 percent, respectively). This reduction was maintained at days 30, 60, and 90. Nearly all events were asymptomatic DVT. The reductions in symptomatic venous thrombosis or pulmonary embolism were not statistically significant in either group. Bleeding complications occurred in 8 percent of each group. Symptomatic intracranial hemorrhage was reported in 1 percent of patients in each group, and major extracranial hemorrhage occurred in 1 percent of patients treated with enoxaparin, but did not occur in the group treated with unfractionated heparin. Minor extracranial bleeding was reported in 5 percent of the enoxaparin group and 6 percent of those treated with unfractionated heparin. The all-cause mortality up to day 90 was 12 percent in each group.

Conclusion: Enoxaparin is preferable to unfractionated heparin for the prevention of venous thromboembolism following acute ischemic stroke.

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Copyright © 2007 by the American Academy of Family Physicians.

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