Content for site developed under the guidance of the TRACK Advisory Council.

Title:   Randomized Comparison of Low-Molecular-Weight Heparin Versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients With Cancer

Objective:  The objective of this study was to determine whether dalteparin is more effective and safer than oral anticoagulant therapy in the prevention of recurrent thromboembolism in patients with cancer who have acute venous thromboembolism.

Study design:  randomized, multicenter, open-label study

Drug names:  dalteparin, warfarin, other vitamin K antagonists

Drug types:  low-molecular-weight heparin (LMWH), vitamin K antagonist

Patient population:  The subjects of this study were patients with active cancer and newly diagnosed, symptomatic proximal deep vein thrombosis (DVT), pulmonary embolism, or both.

Treatment regimens:  Patients were randomized to 1 of 2 groups. The first group received dalteparin 200 IU/kg (max 18,000 IU) once daily for 5 to 7 days and a vitamin K antagonist (in most cases, warfarin) in a dose adjusted to achieve an international normalized ratio (INR) of 2.5 for 6 months. The second group received dalteparin 200 IU/kg (max 18,000 IU) once daily for 1 month followed by 75% to 83% of the full dose (approximately 150 IU/kg) once daily for 5 months.

End Points:  The primary efficacy end point was an episode of documented, symptomatic, recurrent DVT, pulmonary embolism, or both during the 6-month study period. Safety end points were clinically overt bleeding, either major or minor, and death.

Results:  By the end of the 6-month study period, 27 of 336 patients in the dalteparin group and 53 of 336 patients in the oral anticoagulant group had experienced recurrent thromboembolism, for a hazard ratio of 0.48 (95% confidence interval [CI] = 0.30–0.77, P = 0.002). DVT alone occurred in 14 dalteparin patients and 37 oral anticoagulant patients; nonfatal pulmonary embolism occurred in 8 dalteparin patients and 9 oral anticoagulant patients; and fatal pulmonary embolism occurred in 5 dalteparin patients and 7 oral anticoagulant patients. The Kaplan-Meier estimate of the 6-month probability of recurrent thrombosis was 9% in the dalteparin group and 17% in the oral anticoagulant group. Major bleeding occurred in 6% of the dalteparin group and 4% of the oral anticoagulant group (P = 0.27). Mortality rates were 39% in the dalteparin group and 41% in the oral anticoagulant group (P = 0.53).

Conclusions:  In patients with cancer, dalteparin therapy is more effective than and equally as safe as oral anticoagulant therapy in preventing recurrent thromboembolism.

Place in therapy:  Cancer patients with acute thromboembolism are at high risk of recurrence of thromboembolism and therefore are candidates for prophylactic therapy. This study demonstrated that a 6-month regimen of dalteparin therapy is more effective than oral anticoagulant therapy at preventing recurrent thromboembolism in these patients. Dalteparin is particularly effective at preventing DVT but less effective at preventing pulmonary embolism and has no effect on mortality. Because dalteparin therapy is no more likely to result in major bleeding than oral anticoagulant therapy, it can be considered a safe approach in these patients.