Enoxaparin Versus Unfractionated Heparin in the Prevention of Venous Thromboembolism After Acute Ischemic Stroke: Rationale, Design, and Methods of an Open-Label, Randomized, Parallel-Group Multicenter Trial

Background: Small sample size and methodologic limitations make it difficult to interpret and compare trials of low molecular—weight heparin (for example, enoxaparin) versus unfractionated heparin as prophylactic treatment for venous thromboembolism (VTE), that is, deep vein thrombosis and/or pulmonary embolism, in patients with acute ischemic stroke. This prospective, open-label, randomized, parallel-group, multicenter trial is designed to evaluate the efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of VTE after acute ischemic stroke. Methods: Approximately 1760 patients with the diagnosis of acute ischemic stroke accompanied by leg paralysis will be randomly assigned (1:1) within 48 hours of stroke symptoms to receive enoxaparin (40 mg subcutaneously) once daily or unfractionated heparin (5000 U subcutaneously) every 12 hours for 10 ± 4 days. Contrast venography will be used to evaluate asymptomatic patients after treatment for deep vein thrombosis. In addition, diagnostic algorithms will be used to objectively confirm or rule out VTE events for patients in whom upper- or lower-extremity deep vein thrombosis/pulmonary embolism is suggested. Results: The primary efficacy end point measure will be the cumulative occurrence of documented VTE during the initial treatment period. Secondary end points are VTE incidence; neurologic outcome at days 30, 60, and 90; safety; and health care resource use during initial hospitalization and during the 30- and 90-day follow-up periods. Conclusions: This study will provide clinical and health economic data regarding the use of enoxaparin as primary prophylactic treatment of VTE in patients who have had an acute ischemic stroke.