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The PREVAIL trial and low-molecular-weight heparin for prevention of venous thromboembolism.

Marc Fisher MD Kennedy Lees MD Section Editors: 

Patients with stroke are at high risk for venous thromboembolism. Studies of the natural history in the era before widespread use of antiplatelet agents or physical preventive measures reported an incidence of deep vein thrombosis (DVT) of over 50% within the first days.1 A lower incidence might be expected with more aggressive routine acute treatment, including early use of antiplatelet agents, early mobilization, and graduated compression stockings, but the combined control groups of randomized, controlled trials (RCTs) predominantly undertaken in the 1990s still reported an incidence of 37% when DVT was specifically sought.2 Older studies found the incidence of pulmonary embolism (PE) after stroke to be 10% to 20% and to account for up to 10% of all fatalities (including cases in ambulant patients).3 In contrast, symptomatic PE is consistently rarely reported in RCTs in stroke, occurring in just 0.7% of randomized subjects in the control group of trials comparing heparins with antiplatelet therapy.4 However, clinical recognition of PE remains poor. Half of all PEs in one series presented as sudden death.5 Clinically unrecognized PE is also common, with up to 50% of surgical patients with proximal DVT having abnormal ventilation–perfusion lung scans.6 Even if PE is rare, postthrombotic syndrome resulting from venous valvular incompetence causes pain, swelling, and skin changes, including varicose eczema, and may affect over 20% of those with symptomatic DVT within 2 years.

The effectiveness of low-dose unfractionated heparin for prevention of VTE was established in the late 1970s, predominantly in surgical patients but also in stroke.7 The superiority of low-molecular-weight (LMW) heparins over unfractionated heparin in other clinical settings has also been established with advantages including more predictable dose effects, easier administration, and less risk of thrombocytopenia. Two previous RCTs …