Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer

N Engl J Med. 2003 Jul 10;349(2):146-53. doi: 10.1056/NEJMoa025313.

Abstract

Background: Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight heparin with that of an oral anticoagulant agent in preventing recurrent thrombosis in patients with cancer.

Methods: Patients with cancer who had acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both were randomly assigned to receive low-molecular-weight heparin (dalteparin) at a dose of 200 IU per kilogram of body weight subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin alone for six months (200 IU per kilogram once daily for one month, followed by a daily dose of approximately 150 IU per kilogram for five months).

Results: During the six-month study period, 27 of 336 patients in the dalteparin group had recurrent venous thromboembolism, as compared with 53 of 336 patients in the oral-anticoagulant group (hazard ratio, 0.48; P=0.002). The probability of recurrent thromboembolism at six months was 17 percent in the oral-anticoagulant group and 9 percent in the dalteparin group. No significant difference between the dalteparin group and the oral-anticoagulant group was detected in the rate of major bleeding (6 percent and 4 percent, respectively) or any bleeding (14 percent and 19 percent, respectively). The mortality rate at six months was 39 percent in the dalteparin group and 41 percent in the oral-anticoagulant group.

Conclusions: In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding.

Publication types

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

MeSH terms

  • Acenocoumarol / therapeutic use
  • Administration, Oral
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Dalteparin / adverse effects
  • Dalteparin / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Neoplasms / complications*
  • Neoplasms / mortality
  • Pulmonary Embolism / mortality
  • Pulmonary Embolism / prevention & control*
  • Secondary Prevention
  • Survival Analysis
  • Thromboembolism / prevention & control
  • Venous Thrombosis / prevention & control*
  • Warfarin / therapeutic use

Substances

  • Anticoagulants
  • Warfarin
  • Acenocoumarol
  • Dalteparin