A randomized trial evaluating long-term low-molecular-weight heparin therapy for three months vs. intravenous heparin followed by warfarin sodium in patients with current cancer

Abstract number: P1373a

Hull^* R., Pineo^* G. F., Mah^* A. F., Brant^* R. F., For The LITE Investigators† 

^*University of Calgary, Canada;

Background  

Long-term low-molecular-weight heparin (LMWH) has the advantage of once-daily subcutaneous administration as a unit dose per kilogram and anticoagulant monitoring is not required. By comparison, because of the marked intra- and interpatient variability associated with warfarin sodium dosage, oral anticoagulant therapy requires frequent anticoagulant monitoring, using the INR (range INR 2–3) to optimize effectiveness and safety. Meta-analyses suggest in patients with current cancer and deep vein thrombosis, long-term LMWH therapy may be more effective than oral anticoagulant therapy.

Methods  

In a multicenter, randomized (computer generated) clinical trial, we compared subcutaneous therapeutic LMWH (tinzaparin) administered for 84 days vs. initial treatment using UFH for 5 days together with long-term warfarin sodium given to 84 days for the treatment of patients with objectively diagnosed proximal deep-vein thrombosis. Follow-up of objectively documented clinical outcomes occurred at 84 days and 1 years following randomization. Safety was documented using objective criteria for bleeding complications.

Results  

Eighty patients received long-term LMWH and 87 received IV heparin/long-term warfarin. At days 84 and 365, respectively, 5 (6.3%) and 6 (7.5%) of 80 patients in the LMWH group vs. 10 (11.5%) and 16 (18.4%) (Long-rank test: p = 0.034) of 87 patients in the warfarin group suffered recurrent VTE [Fig. 1]. At days 84 and 365, death occurred in 18 (22.5%) and 43 (53.8%) patients in the LMWH group and 19 (21.8%) and 48 (55.2%) patients in the warfarin group. Haemorrhagic complications during the 84-day treatment interval occurred in 24 of 80 (30.0%) patients receiving LMWH vs. 24 of 87 (27.6%) patients receiving warfarin; of these patients who bled, 5 (6.3%) and 7 (8.0%) had major bleeding (RR = 0.78, CI 0.26–2.35) and 19 (23.8%) and 17 (19.5%) had minor bleeding, respectively.

Discussion  

LMWH provides cancer patients with more effective therapy without loss of safety.