Dalteparin, a low-molecular-weight heparin (Fragmin, Pharmacia), is more effective than oral coumarin derivatives in reducing the risk of recurrent thromboembolism in patients with cancer, without increasing the risk of bleeding, according to a report in The New England Journal of Medicine for July 10th.
The risk of recurrent thromboembolism and bleeding is increased when patients have cancer, Dr. Mark N. Levine and associates point out. Secondary prophylaxis with dalteparin is attractive because of its predictable pharmacokinetics properties and drug interactions. Absorption is not a concern because it is administered subcutaneously rather than orally, and laboratory monitoring is not routinely required.In a multinational, open-label trial, Dr. Levine, of McMaster University in Hamilton, Ontario, Canada, and his team randomly assigned 676 cancer patients to a dalteparin group or a coumarin-derivative group. The patients had experienced a symptomatic proximal deep-vein thrombosis, pulmonary embolism or both.Patients in both groups were treated with subcutaneous dalteparin 200 IU/kg once daily for 5 to 7 days. Those assigned to an oral anticoagulant were switched to warfarin or acenocoumarol at a dose targeted to an international normalized ratio of 2.5. Those in the dalteparin group continued dalteparin 200 IU/kg daily for 1 month, followed by a daily dose of approximately 150 IU/kg for 5 months. Recurrent venous thromboembolism was diagnosed during the 6-month trial in 27 of 336 patients in the dalteparin group and in 53 of 336 in the oral-anticoagulant group, resulting in a hazard ratio of 0.48 (p = 0.002) for the dalteparin group.Six percent in the dalteparin group and 4% the oral anticoagulant group experienced major bleeding (p = 0.27), while 14% and 19%, respectively, experienced any bleeding (p = 0.09). Mortality rates did not differ between groups (p = 0.53).Dr. Levine’s group notes that “long-term self-injection of dalteparin was acceptable to our patients, and it significantly reduced the risk of recurrent venous thromboembolism without increasing the risk of bleeding.”Describing the study as “well-designed,” Dr. Rodger L. Bick writes in a Journal editorial that “low-molecular-weight heparin should become the therapeutic and prophylactic agent of choice in cancer-associated thromboembolic disease.”Furthermore, adds the physician from the University of Texas Southwestern Medical School in Dallas, the expense of dalteparin is offset by reduced medical care costs and the need to monitor INR ratio when treating with other anticoagulants.(Source: N Engl J Med 2003;349:109-111,146-153: Reuters Health: July 10, 2003: Oncolink)