Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism.
OBJECTIVE
Experimental studies and indirect clinical evidence suggest that low molecular weight heparins may have antineoplastic effects. We investigated the influence of a low molecular weight heparin dalteparin on the survival of patients with active cancer and acute venous thromboembolism.


METHODS
Survival data were examined in a posthoc analysis in patients with solid tumors and venous thromboembolism who were randomly assigned to dalteparin or a coumarin derivative for 6 months in a multicenter, open-label, randomized, controlled trial. All-cause mortality at 12 months was compared between treatment groups in patients with and without metastatic malignancy. The effect of dalteparin on survival was compared between the two patient subgroups.


RESULTS
During the 12-month follow-up period, 356 of 602 patients with solid tumors and acute venous thromboembolism died. Among patients without metastatic disease, the probability of death at 12 months was 20% in the dalteparin group, as compared with 36% in the oral anticoagulant group (hazard ratio, 0.50; 95% CI, 0.27 to 0.95; P = .03). In patients with metastatic cancer, no difference in mortality between the treatment groups was observed (72% and 69%, respectively; hazard ratio, 1.1; 95% CI, 0.87 to 1.4; P = .46). The observed effects of dalteparin on survival were statistically significantly different between patients with and without metastatic disease (P = .02).


CONCLUSIONS
The use of dalteparin relative to coumarin derivatives was associated with improved survival in patients with solid tumors who did not have metastatic disease at the time of an acute venous thromboembolic event. Additional studies are warranted to investigate these findings.
Lee
Agnes Y Y
AY
Hamilton Health Science, Henderson Hospital, Room 9, 90 Wing, 711 Concession St, Hamilton, ON L8V 1C3, Canada.
Rickles
Frederick R
FR
Julian
Jim A
JA
Gent
Michael
M
Baker
Ross I
RI
Bowden
Chris
C
Kakkar
Ajay K
AK
Prins
Martin
M
Levine
Mark N
MN
D000208:Acute Disease; D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D003374:Coumarins / Q000627:therapeutic use*; D017985:Dalteparin / Q000627:therapeutic use*; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D016019:Survival Analysis; D013923:Thromboembolism / Q000188:drug therapy* / Q000209:etiology; D016896:Treatment Outcome
D000925:Anticoagulants; D003374:Coumarins; D006495:Heparin, Low-Molecular-Weight; C030123:coumarin; D017985:Dalteparin