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Prof. Steen Dalby Kristensen ,
Dalteparin is superior to standard-dose coumarins in patients with malignant disease and deep venous thrombosis and/or pulmonary embolism.
Venous thromboembolism (VTE) a rather frequent and serious event in patients with cancer and may be the first sign of a malignant disease. The treatment of VTE in these patients is anti-coagulation with aspirin, heparin (unfractionated or low-molecular weight (LMWH) followed by low- or standard dose coumarins or fibrinolytic therapy. These treatments are less efficient in cancer patients than in patients with venous thromboembolism without malignant disease, and the incidence of bleeding is higher in patients with cancer.
Long-term treatment with LMWH is also an option. Dalteparin is a LMWH that is widely used in venous and arterial thrombosis. The effect of dalteparin on the recurrence of venous thromboembolism was tested against coumarins in a recent, randomized, multicenter trial. 676 patients with cancer and deep venous thrombosis and/or pulmonary embolism were in an open-label design randomized to either dalteparin subcutaneously 200U/kg once daily for 5-7 days and a coumarin derivative for 6 months (target INR: 2.5) or dalteparin 200 U/kg once daily for one month followed by 150 U/kg subcutaneously once daily for 5 month. The diagnosis of deep venous thrombosis was verified by compression ultrasonography or by contrast venography. Pulmonary embolism was verified by ventilation-reperfusion scan, helical CT-scan or pulmonary angiography.
The primary endpoint of the study was the occurrence of a new incidence of VTE. The patients were followed for 6 month or until death occurred. 27 of the 336 patients in the dalteparin group and 53 of the 336 patients in the oral-anticoagulant group developed VTE (9% vs 17%, hazard ratio, 0.48; p=0.002). There was no statistical difference in the rate of bleeding episodes between the two groups. The mortality rate was 39% in the dalteparin and 41% in the oral-anticouagulant group. The patients were instructed in self-injection of dalteparin. INR was measured at least once every two weeks and the average INR obtained was 2.5. Patients with body weight less than 40 kg, platelet count below 75,000 per cubic millimetre, creatinine levels above 3 times the upper limit of the normal range or with a recent episode of serious bleeding were excluded from the trial.
The study suggests that long-term self-injection of dalteparin is the treatment of choice in many patients with cancer and a diagnosis of venous thrombolism.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.
1. Lee AYY, Levine MN, Baker RI et al. Low-molecular weight heparin versus coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349: 146-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12853587&dopt=Abstract
Steen Dalby Kristensen and Jens Flensted Lassen Member and Vice-chairman of the Working Group on Thrombosis. ESC WG on Thrombosis University Department of Cardiology Skejby Hospital DK-8200 Aarhus N Denmark
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