Clinical Epidemiology Program, Ottawa Hospital Research Institute, 501 Smyth Box 511, Ottawa, ON K1H 8L6, Canada; Faculty of Medicine, University of Ottawa, 451 Smyth Rd #2044, Ottawa, ON K1H 8M5, Canada.
Clinical Epidemiology Program, Ottawa Hospital Research Institute, 501 Smyth Box 511, Ottawa, ON K1H 8L6, Canada.
Thromb Res. 2020 Nov;195:103-113. doi: 10.1016/j.thromres.2020.07.008. Epub 2020 Jul 8.
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.
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.
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.
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.
低分子肝素（LMWH）的治疗效果可能不仅限于预防血栓形成，临床前证据表明其具有抗转移特性。然而，关于该主题的临床证据仍然存在争议。对临床前证据进行系统评价可能有助于阐明这种矛盾证据的原因。本系统评价的目的是评估 LMWH 在实体瘤动物模型中的抗转移特性。
从建库到 2020 年 5 月 12 日，我们在 MEDLINE、Embase、Web of Science 和 PubMed 上进行了检索。所有文章均由两人独立筛选。纳入了比较 LMWH 与安慰剂或无治疗组在实体瘤动物模型中的研究。主要结局是转移负担。次要结局包括原发肿瘤生长和死亡率。使用改良的 Cochrane 偏倚风险工具对偏倚风险进行了重复评估。
本综述共纳入了 42 项研究。给予 LMWH 可显著降低转移负担（SMD -2.18；95%CI -2.66 至 -1.70）。此外，给予 LMWH 还与原发肿瘤生长（SMD -1.95；95%CI -2.56 至 -1.34）和死亡风险（RR 0.39；95%CI 0.16-0.97）降低显著相关。所有纳入的研究在至少一个方法学标准上被认为存在不确定偏倚风险。
我们的结果表明，LMWH 可有效降低实体瘤恶性肿瘤的动物模型中的转移负担和肿瘤生长。与临床证据相矛盾的原因需要进一步探讨。
