Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study

Arch Intern Med. 2002 Aug 12-26;162(15):1729-35. doi: 10.1001/archinte.162.15.1729.

Abstract

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / therapeutic use*
  • Dose-Response Relationship, Drug
  • Embolism / mortality
  • Embolism / prevention & control*
  • Endpoint Determination
  • Female
  • Follow-Up Studies
  • Hemorrhage / chemically induced
  • Heparin, Low-Molecular-Weight / therapeutic use*
  • Humans
  • International Normalized Ratio
  • Male
  • Middle Aged
  • Neoplasms / complications*
  • Neoplasms / drug therapy*
  • Neoplasms / mortality
  • Recurrence
  • Survival Analysis
  • Treatment Outcome
  • Venous Thrombosis / mortality
  • Venous Thrombosis / prevention & control*
  • Warfarin / therapeutic use*

Substances

  • Anticoagulants
  • Heparin, Low-Molecular-Weight
  • Warfarin