Meta-Analysis Shows Heparin Administration Decreases the Risk of Venous Thromboembolism Among Ambulatory Patients With Cancer

Sahar Memar Montazerin, MD
By Sahar Memar Montazerin, MD on

A recent study by Dr. Holger J Schünemann, published in THE LANCET Haematology, demonstrated that, in patients with solid tumors, venous thromboembolic events can be reduced by administering low-molecular-weight heparin without an increase in the risk of bleeding complications or a change in the survival rate.

Given the increase in cancer incidence over the past couple of years and the association between solid tumors and venous thromboembolic events, patients with solid tumors are likely to benefit from anticoagulant use. There are speculations regarding the antitumor effects of heparins and whether they may improve outcomes in this population. However, bleeding complications and heparin-induced thrombocytopenia are factors that make these medications unfavorable, particularly considering the susceptibility of cancer patients for bleeding complications. To identify how this risk-benefit tradeoff affects patients with solid tumors, Dr. Holger J Schunemman and colleagues performed an individual participant data meta­-analysis of the previous randomized trials.

The study included individual data from 14 randomized control trials comparing heparins with placebo or the standard of care among ambulant patients with solid tumors who had no indication for anticoagulant use. The primary outcome included all-cause mortality and venous thromboembolic occurrence. Major and minor bleeding and thrombocytopenia were the secondary outcomes of interest.

A total of 8278 participants were equally distributed in the low-molecular-weight heparin group and control group. The adjusted relative risk (RR) of mortality at 1 year was reported 0·99 (95% Confidence Interval (CI): 0·93–1·06). Although not a significant finding, these results contradict the theory that heparin induces antitumor effects. However, heparins were associated with a significant reduction in venous thromboembolic events (adjusted RR: 0·58; [95% CI: 0·47–0·71]) without a significant increase in major bleeding complications (adjusted RR: 1·27; [95% CI: 0·92–1·74]). Minor bleeding events, however, slightly increased after anticoagulation with heparin (adjusted RR: 1·34; [95% CI: 1·19–1·51]). Results stratified by type of cancer indicated that patients with lung cancer were more likely to benefit from heparin administration with regard to venous thromboembolism occurrence when compared to all other types of cancer (RR: 0·59; [95% CI: 0·42–0·81]). 

Results from this meta-analysis may provide evidence for the development of clinical practice guidelines for venous thromboprophylaxis among patients with cancer. Future research is warranted to identify the effects of low-molecular-­weight heparin by type, dose, and schedule.


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