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OBJECTIVE	Low-molecular-weight heparin is recommended over warfarin for the treatment of acute venous thromboembolism ( VTE ) in patients with active cancer largely based on results of a single , large trial .
OBJECTIVE	To study the efficacy and safety of tinzaparin vs warfarin for treatment of acute , symptomatic VTE in patients with active cancer .
METHODS	A randomized , open-label study with blinded central adjudication of study outcomes enrolled patients in 164 centers in Asia , Africa , Europe , and North , Central , and South America between August 2010 and November 2013 .
METHODS	Adult patients with active cancer ( defined as histologic diagnosis of cancer and receiving anticancer therapy or diagnosed with , or received such therapy , within the previous 6 months ) and objectively documented proximal deep vein thrombosis ( DVT ) or pulmonary embolism , with a life expectancy greater than 6 months and without contraindications for anticoagulation , were followed up for 180 days and for 30 days after the last study medication dose for collection of safety data .
METHODS	Tinzaparin ( 175 IU/kg ) once daily for 6 months vs conventional therapy with tinzaparin ( 175 IU/kg ) once daily for 5 to 10 days followed by warfarin at a dose adjusted to maintain the international normalized ratio within the therapeutic range ( 2.0-3 .0 ) for 6 months .
METHODS	Primary efficacy outcome was a composite of centrally adjudicated recurrent DVT , fatal or nonfatal pulmonary embolism , and incidental VTE .
METHODS	Safety outcomes included major bleeding , clinically relevant nonmajor bleeding , and overall mortality .
RESULTS	Nine hundred patients were randomized and included in intention-to-treat efficacy and safety analyses .
RESULTS	Recurrent VTE occurred in 31 of 449 patients treated with tinzaparin and 45 of 451 patients treated with warfarin ( 6-month cumulative incidence , 7.2 % for tinzaparin vs 10.5 % for warfarin ; hazard ratio [ HR ] , 0.65 [ 95 % CI , 0.41-1 .03 ] ; P = .07 ) .
RESULTS	There were no differences in major bleeding ( 12 patients for tinzaparin vs 11 patients for warfarin ; HR , 0.89 [ 95 % CI , 0.40-1 .99 ] ; P = .77 ) or overall mortality ( 150 patients for tinzaparin vs 138 patients for warfarin ; HR , 1.08 [ 95 % CI , 0.85-1 .36 ] ; P = .54 ) .
RESULTS	A significant reduction in clinically relevant nonmajor bleeding was observed with tinzaparin ( 49 of 449 patients for tinzaparin vs 69 of 451 patients for warfarin ; HR , 0.58 [ 95 % CI , 0.40-0 .84 ] ; P = .004 ) .
CONCLUSIONS	Among patients with active cancer and acute symptomatic VTE , the use of full-dose tinzaparin ( 175 IU/kg ) daily compared with warfarin for 6 months did not significantly reduce the composite measure of recurrent VTE and was not associated with reductions in overall mortality or major bleeding , but was associated with a lower rate of clinically relevant nonmajor bleeding .
CONCLUSIONS	Further studies are needed to assess whether the efficacy outcomes would be different in patients at higher risk of recurrent VTE .
BACKGROUND	clinicaltrials.gov Identifier : NCT01130025 .

