A Comparison of the Safety and Efficacy of Oral Antiocoagulation for the Treatment of Venous Thromboembolic Disease in Patients with or without Malignancy

Summary

The optimal long-term treatment of acute venous thromboembolism (VTE) in patients with malignancy remains undefined. In particular, based on current evidence, it is uncertain whether secondary prophylaxis using standard intensity oral anticoagulant therapy is associated with higher risks of bleeding and recurrent thrombosis in patients with cancer than in those without cancer. This study compared the outcome of anticoagulation courses in 95 patients with malignancy with those of 733 patients without malignancy. All patients were participants in a large, nation-wide population study and were prospectively followed from the initiation of their oral anticoagulant therapy.

Based on 744 patient-years of treatment and follow-up, the rates of major (5.4% vs 0.9%), minor (16.2% vs 3.6%) and total (21.6% vs 4.5%) bleeding were statistically significantly higher in cancer patients compared with patients without cancer. Bleeding was also a more frequent cause of early anticoagulation withdrawal in patients with malignancy (4.2% vs. 0.7%; p <0.01; RR 6.2 (95%CI 1.95-19.4). There was a trend towards a higher rate of thrombotic complications in cancer patients (6.8% vs. 2.5%; p = 0.058; RR 2.5 [CI 0.96-6.5]) but this did not achieve statistical significance. In the group of patients with cancer, the bleeding rate was high across the different INR categories and was independent of the temporally associated International Normalized Ratio (INR). In contrast, the bleeding rate was increased only with INR values greater than 4.5 in the group of patients without cancer. The rate of thrombotic events was significantly higher in both cohorts when the INR was less than 2.0.

In conclusion, patients with malignancy treated with oral anticoagulants have a higher rate of bleeding and possibly an increased risk of recurrent thrombosis compared with patients without malignancy. Safer and more effective anticoagulant therapy is needed for this challenging group of patients.

Key words

Oral anticoagulation - DVT - cancer - safety

• References

• 1 Hyers TM, Agnelli G, Hull RD. et al. Antithrombotic therapy for venous thromboembolic disease. Chest 1998; 114: S561-8.
• 2 Kearon C, Hirsh J. Current concepts: management of anticoagulation before and after elective surgery. N Engl J Med 1997; 336: 1506-11.
• 3 Moore F, Osteen R, Karp D, Steele G, Wilson R. Anticoagulants, venous thromboembolism and the cancer patient. Arch Surg 1981; 116: 405-7.
• 4 Clarke-Pearson DL, Synan IS, Creasman WT. Anticoagulation therapy for venous thromboembolism in patients with gynaecologic malignancy. Am J Obstet Gynecol 1983; 147: 369-75.
• 5 Chan A, Woodruff RK. Complications and Failure of Anticoagulation Therapy in the Treatment of Venous Thromboembolism in Patients with Disseminated Malignancy. Aust N Z J Med 1992; 22: 119-22.
• 6 Monreal M, Roncales FJ, Ruiz J. et al. Secondary prevention of venous thromboembolism: A role for low-molecular-weight heparin. Haemostasis 1998; 28: 236-43.
• 7 Bona RD, Sivjee KY, Hickey AD, Wallace DM, Wajcs SB. The efficacy and safety of oral anticoagulation in patients with cancer. Thromb Haemost 1995; 74: 1055-8.
• 8 Cohen JR, Tenenbaum N, Citron M. Greenfield Filter As Primary Therapy for Deep Venous Thrombosis and/or Pulmonary Embolism in Patients with Cancer. Surgery 1991; 109: 12-5.
• 9 Palareti G, Leali N, Coccheri S. et al. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Lancet 1996; 348: 423-8.
• 10 Palareti G, Manotti C, Dangelo A. et al. Thrombotic events during oral anticoagulant treatment: results of the inception-cohort, prospective, collaborative ISCOAT study. Thromb Haemost 1997; 78: 1438-43.
• 11 Rosendaal FR, Cannegieter SC, Vandermeer FJM, Briet E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993; 69: 236-7.
• 12 Levitan N, Dowlati A, Remick SC. et al. Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy-Risk analysis using Medicare claims data. Medicine 1999; 78: 285-91.
• 13 Gitter MJ, Jaeger TM, Petterson TM, Gersh BJ, Phil D, Silverstein MD. Bleeding and thromboembolism during anticoagulant therapy: a population-based study in Rochester, Minnesota. Mayo Clin Proc 1995; 70: 725-33.
• 14 Prandoni P, Lensing AWA, Cogo A. et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996; 125: 1.
• 15 Sack G, Levin J, Bell W. Trousseau’s syndrome and other manifestations of chronic disseminated coagulopathy in patients with neoplasms: clinical, pathophysiologic, and therapeutic features. Medicine 1977; 56: 1-37.
• 16 Bell W, Starksen N, Tong S, Porterfield J. Trousseau’s syndrome. Devastating coagulopathy in the absence of heparin. Am J Med 1985; 79: 423-30.
• 17 Ambrus J, Ambrus C, Mink I, Pickern J. Causes of death in cancer patients. J Med 1975; 06: 61-4.