The effect of low-molecular-weight heparin on cancer survival. A systematic review and meta-analysis of randomized trials

Background: Low-molecular-weight heparins (LMWH) have an antitumor effect in vitro and in experimental animal models of malignancy. Retrospective data suggest that it might improve survival in cancer patients. Objectives: To evaluate the effect of LMWH compared to placebo or no anticoagulant intervention on the survival of cancer patients. Methods: We conducted a systematic review of randomized trials specifically evaluating the impact of LMWH on the survival of cancer patients. Data sources were: MEDLINE, EMBASE, HealthSTAR, Cochrane library, gray literature and cross-referencing from reference lists. Data extraction was performed by one reviewer, and accuracy was independently verified by a second reviewer. Meta-analysis was conducted using: (i) odds ratio (OR) and relative risk (RR); (ii) survival rates using censored endpoints; and (iii) hazard ratios (HR). Results: The pooled HR in all patients was 0.83 (95% CI 0.70-0.99; P = 0.03), and in patients with advanced disease it was 0.86 (95% CI 0.74-0.99; P = 0.04), both in favor of the LMWH group. The results of the OR, RR and survival meta-analysis consistently favored the LMWH group. Sensitivity analyses according to tumor type were not conducted, because of a lack of information. Conclusions: LMWH improves overall survival in cancer patients, even in those with advanced disease. Additional trials are required to define the tumor types, disease stages and dosing schedules most likely to provide the greatest survival benefit.