Low molecular weight heparins could be important in cancer

Editor—Kakkar and Williamson clearly state the need for well conducted prospective clinical trials to evaluate the potential role of low molecular weight heparins in improving survival in cancer patients.¹

In the absence of properly designed trials, indirect data can be extrapolated from trials comparing low molecular weight heparins and unfractionated heparin in the treatment of venous thromboembolism. Reduced mortality in patients with venous thromboembolism who were treated with low molecular weight heparins seemed to be confined to patients with cancer.²

In a meta-analysis of randomised clinical trials(1723 subjects overall: 848 in the low molecular weight heparin group and 875 in the unfractionated heparin group), we evaluated mortality in the first 15 days of treatment, when a true effect of low molecular weight heparins would be expected, and in the three months of subsequent oral anticoagulation.³ After a follow up of three months, overall mortality was 3.3% in the low molecular weight heparin group and 5.9% in the unfractionated heparin group (relative risk 0.51, 95% confidence interval 0.2 to 0.9, P<0.01). Although there was no significant difference in overall mortality in the first 15 days, the difference during oral anticoagulation was significant (2.5% v 4.5%; 0.48, 0.2 to 0.8, P<0.03). In a separate analysis in patients with a diagnosis of cancer at the time of initial diagnosis of venous thromboembolism, 1.3% of patients in the low molecular weight heparin group died during the first 15 days of treatment compared with 2.5% in the unfractionated heparin group (0.5, 0.01 to 7.7, P=0.52). The difference in mortality in patients with cancer during the 16-90 day follow up period of oral anticoagulation was significant: 12% in the low molecular weight heparin group and 26% in the unfractionated heparin group (0.33, 0.1 to 0.8, P<0.01). During the combined period of heparin and oral anticoagulation therapy, mortality was 14% in patients with cancer treated with low molecular weight heparin and 28% in those treated with unfractionated heparin (0.33, 0.1 to 0.8, P<0.01). Mortality in patients without cancer was not significantly different between the groups (1.9% v 2.6%; 0.72, 0.3 to 0.6, P=0.4).

Our observation does not support the hypothesis that the reduction in death in patients with cancer is due to an effect of low molecular weight heparins in preventing thromboembolism. No difference in mortality from all causes was observed in patients without cancer. The cause of reduced mortality in cancer patients treated with low molecular weight heparins is therefore difficult to explain.