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A Randomized Controlled Study

Guy Meyer, MD; Zora Marjanovic, MD; Judith Valcke, MD; Bernard Lorcerie, MD; Yves Gruel, MD; Philippe Solal-Celigny, MD; Christine Le Maignan, MD; Jean Marc Extra, MD; Paul Cottu, MD; Dominique Farge, MD

Arch Intern Med. 2002;162:1729-1735.

Background  The use of warfarin sodium for treating venous thromboembolism in patients with cancer is associated with a significant risk of recurrence and bleeding. The use of low-molecular-weight heparin sodium for secondary prevention of venous thromboembolism in cancer patients may reduce the complication rate.

Objective  To determine whether a fixed dose of subcutaneous low-molecular-weight heparin is superior to oral warfarin for the secondary prophylaxis of venous thromboembolism in patients with cancer and venous thromboembolism.

Methods  In a randomized, open-label multicenter trial performed between April 1995 and March 1999, we compared subcutaneous enoxaparin sodium (1.5 mg/kg once a day) with warfarin given for 3 months in 146 patients with venous thromboembolism and cancer.

Main Outcome Measure  A combined outcome event defined as major bleeding or recurrent venous thromboembolism within 3 months.

Results  Of the 71 evaluable patients assigned to receive warfarin, 15 (21.1%; 95% confidence interval [CI], 12.3%-32.4%) experienced one major outcome event compared with 7 (10.5%) of the 67 evaluable patients assigned to receive enoxaparin (95% CI, 4.3%-20.3%; P = .09). There were 6 deaths owing to hemorrhage in the warfarin group compared with none in the enoxaparin group. In the warfarin group, 17 patients (22.7%) died (95% CI, 13.8%-33.8%) compared with 8 (11.3%) in the enoxaparin group (95% CI, 5.0%-21.0%; P = .07). No difference was observed regarding the progression of the underlying cancer or cancer-related death.

Conclusions  These results confirm that warfarin is associated with a high bleeding rate in patients with venous thromboembolism and cancer. Prolonged treatment with low-molecular-weight heparin may be as effective as oral anticoagulants and may be safer in these cancer patients.

From the Department of Respiratory and Critical Care Medicine, Hôpital Européen Georges Pompidou, Paris V University, Paris, France (Drs Meyer and Valcke); Department of Internal Medicine, Hôpital Saint Louis, Paris VII University, Paris (Drs Marjanovic and Farge); Department of Internal Medicine, Hôpital du Bocage, and Dijon University, Dijon, France (Dr Lorcerie); Department of Haematology, Hôpital Trousseau, and Tours University, Tours, France (Dr Gruel); Department of Medical Oncology, Clinique Victor Hugo, Le Mans, France (Dr Solal-Celigny); Department of Medical Oncology, Hôpital Européen Georges Pompidou, Paris (Dr Le Maignan); and Department of Medical Oncology, Hôpital Saint-Louis, Paris (Drs Extra and Cottu).

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