Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study.
BACKGROUND
The use of warfarin sodium for treating venous thromboembolism in patients with cancer is associated with a significant risk of recurrence and bleeding. The use of low-molecular-weight heparin sodium for secondary prevention of venous thromboembolism in cancer patients may reduce the complication rate.


OBJECTIVE
To determine whether a fixed dose of subcutaneous low-molecular-weight heparin is superior to oral warfarin for the secondary prophylaxis of venous thromboembolism in patients with cancer and venous thromboembolism.


METHODS
In a randomized, open-label multicenter trial performed between April 1995 and March 1999, we compared subcutaneous enoxaparin sodium (1.5 mg/kg once a day) with warfarin given for 3 months in 146 patients with venous thromboembolism and cancer.


METHODS
A combined outcome event defined as major bleeding or recurrent venous thromboembolism within 3 months.


RESULTS
Of the 71 evaluable patients assigned to receive warfarin, 15 (21.1%; 95% confidence interval [CI], 12.3%-32.4%) experienced one major outcome event compared with 7 (10.5%) of the 67 evaluable patients assigned to receive enoxaparin (95% CI, 4.3%-20.3%; P =.09). There were 6 deaths owing to hemorrhage in the warfarin group compared with none in the enoxaparin group. In the warfarin group, 17 patients (22.7%) died (95% CI, 13.8%-33.8%) compared with 8 (11.3%) in the enoxaparin group (95% CI, 5.0%-21.0%; P =.07). No difference was observed regarding the progression of the underlying cancer or cancer-related death.


CONCLUSIONS
These results confirm that warfarin is associated with a high bleeding rate in patients with venous thromboembolism and cancer. Prolonged treatment with low-molecular-weight heparin may be as effective as oral anticoagulants and may be safer in these cancer patients.
Meyer
Guy
G
Department of Respiratory and Critical Care Medicine, Hôpital Européen Georges Pompidou, Paris V University, France. guy.meyer@hop.egp.ap-hop-paris.fr
Marjanovic
Zora
Z
Valcke
Judith
J
Lorcerie
Bernard
B
Gruel
Yves
Y
Solal-Celigny
Philippe
P
Le Maignan
Christine
C
Extra
Jean Marc
JM
Cottu
Paul
P
Farge
Dominique
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004617:Embolism / Q000401:mortality / Q000517:prevention & control*; D023381:Endpoint Determination; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D012008:Recurrence; D016019:Survival Analysis; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000401:mortality / Q000517:prevention & control*; D014859:Warfarin / Q000627:therapeutic use*
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D014859:Warfarin