Selecting an anticoagulant for recurrent venous thromboembolism in cancer

Susan Goodin
American Journal of Health-system Pharmacy: AJHP 2005 November 15, 62 (22 Suppl 5): S10-3

PURPOSE: The thrombogenicity of newer anticancer agents and the challenges associated with managing cancer patients on warfarin have led to the evaluation of the low-molecular-weight heparins (LMWHs) for primary and secondary prophylaxis in this high-risk patient population.

SUMMARY: The first published trial of LMWH in cancer compared three months of warfarin therapy with enoxaparin in cancer patients with proximal deep venous thrombosis (DVT), pulmonary embolism (PE), or both. All patients received four days of enoxaparin 1.5 mg/kg and were then randomized to continue receiving enoxaparin or begin warfarin therapy. Due to inadequate patient enrollment, no statistically significant differences were detected between the two treatment groups. In a similar patient population, the Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) trial evaluated the use of long-term dalteparin for the prevention of recurrent venous thromboembolism (VTE) in patients with cancer. Cancer patients with proximal DVT, PE, or both were randomized to initial treatment with dalteparin followed by either six months of oral anticoagulant therapy or dalteparin monotherapy. The primary outcome was symptomatic, recurrent VTE, and secondary outcomes were bleeding events and survival time. The cumulative risk of recurrent VTE at six months was reduced from 17% in the oral anticoagulant group to 9% in the dalteparin group, a risk reduction of 52% (p=0.002). No significant differences in bleeding events or overall mortality occurred between the groups. Recent recommendations from the American College of Chest Physicians on the treatment of cancer-associated thrombosis are based in part on data from the CLOT trial and support the use of dalteparin and tinzaparin in the long-term treatment of patients with DVT and cancer. Finally, results of recent trials support the concept that antithrombotic therapy with dalteparin or nadroparin may have an antineoplastic effect, resulting in improved survival time. However, these results require further validation.

CONCLUSION: Despite the absence of oncology-specific guidelines for cancer-associated thrombosis, pharmacists now have a number of new tools available for selecting an anticoagulant, including results from several clinical trials with LMWHs and recent reports from national meetings.

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