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Am Fam Physician. 2001;64(6):1073-1076

Deep venous thrombosis (DVT) is often treated in the hospital with five to 10 days of unfractionated heparin. The activated partial thromboplastin time is maintained at more than 1.5 times its control value. An alternative initial treatment is five to 10 days of weight-adjusted low-molecular-weight heparin. Both initial regimens are followed by at least three months of oral anticoagulant therapy. Studies supporting the use of low-molecular-weight heparin to treat DVT have been small and often have excluded patients with pulmonary embolism. Because of this, Merli and associates compared the use of continuously infused unfractionated heparin with two weight-adjusted dosages of enoxaparin, administered subcutaneously once or twice daily.

In a partially blinded, international, multicenter clinical trial, patients 18 years and older were randomized to treatment with enoxaparin or unfractionated heparin. Patients with symptomatic lower-extremity DVT confirmed by venography or ultrasonography, symptomatic pulmonary embolism confirmed by high-probability ventilation-perfusion scanning or positive pulmonary angiography with confirmation of lower-extremity DVT were included in the trial. Patients treated with enoxaparin received 1.0 mg per kg of body weight twice daily or 1.5 mg per kg once daily. Treatment was continued for at least five days, and warfarin therapy was started within 72 hours of administration of the initial study drug. Patients were discharged from the hospital after the International Normalized Ratio was between 2.0 and 3.0 on two consecutive days. Oral anticoagulation was continued for at least three months.

The primary clinical end point was recurrent DVT or pulmonary embolism within three months of randomization. Of the 740 evaluable patients who completed the protocol, 694 (80.8 percent) initially presented with proximal lower-extremity DVT. A total of 287 patients also had documented pulmonary embolism at presentation. Venous thromboembolism recurrence within the three-month follow-up period was similar (2.9 to 4.4 percent) among all three treatment groups. Cancer and symptomatic pulmonary embolism were significant risk factors for recurrence, regardless of treatment. Obesity was also a risk factor for recurrence in the patients treated with enoxaparin. There was little difference in adverse events or deaths among the three treatment groups. The incidence of thrombocytopenia was similar in all groups.

The authors conclude that enoxaparin administered subcutaneously once or twice daily was as effective and safe as unfractionated heparin in preventing recurrence of venous thromboembolic disease. Patients with cancer and symptomatic pulmonary embolism were more likely to develop recurrence of venous thromboembolism regardless of treatment group.

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Copyright © 2001 by the American Academy of Family Physicians.

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