A systematic review on the efficacy and safety of low molecular weight heparin as an anticancer therapeutic in preclinical animal models

Objective The therapeutic effects of low molecular weight heparins (LMWH) may extend past thrombosis prevention, with preclinical evidence demonstrating anti-metastatic properties. Clinical evidence on the topic, however, remains controversial. A systematic review of preclinical evidence may help elucidate reasons for this contradictory evidence. The objective of our systematic review is to assess the anti-metastatic properties of LMWHs in solid tumour animal models. Methods MEDLINE, Embase, Web of Science and PubMed were searched from inception to May 12th, 2020. All articles were screened independently and in duplicate. Studies that compared LMWH to a placebo or no treatment arm in solid tumour animal models were included. The primary outcome was the burden of metastasis. Secondary outcomes included primary tumour growth and mortality. The risk of bias was assessed in duplicate using a modified Cochrane Risk of Bias tool. Results Forty-two studies were included in the review. Administration of a LMWH was associated with a significant decrease in the burden of metastasis (SMD −2.18; 95% CI −2.66 to −1.70). Additionally, the administration of a LMWH was also associated with a significant reduction in primary tumour growth (SMD −1.95; 95% CI −2.56 to −1.34) and risk of death (RR 0.39; 95% CI 0.16–0.97). All included studies were deemed to be at an unclear risk of bias for at least one methodological criterion. Conclusions Our results demonstrate that LMWH can effectively reduce metastatic burden and reduce tumour growth in preclinical animal models of solid tumour malignancies. Reasons for the contradiction with clinical evidence require further exploration.