The effect of low molecular weight heparin on survival in cancer patients: an updated systematic review and meta‐analysis of randomized trials

Abstract

To cite this article: Sanford D, Naidu A, Alizadeh N, Lazo-Langner A. The effect of low molecular weight heparin on survival in cancer patients:an updated systematic review and meta-analysis of randomized trials. J Thromb Haemost 2014; 12: 1076-85.Summary. Background: Tumors may exploit the coagulation system to enhance the survival and dissemination of cancer cells. Some studies have suggested that heparin and low molecular weight heparin (LMWH) have antitumor effects. We reported a previous meta-analysis that suggested a modest improvement in overall survival with the use of LMWH in patients with cancer. Herein, we present the results of an updated systematic review and meta-analysis. Objective: To evaluate the effect of LMWH as compared with placebo or no anticoagulant on the overall survival in patients with solid cancers. Methods: We conducted a systematic review and metaanalysis of randomized trials evaluating the use of LMWH vs. placebo or no anticoagulant in cancer patients without venous thrombosis. A meta-analysis was conducted with a random-effects model, and data were analyzed by the use of odds ratios (ORs) and relative risks (RRs) calculated for 1-year overall mortality. Results: We identified 724 potentially relevant studies, nine of which met our inclusion criteria, and reported data on 1-year overall mortality. Studies were heterogeneous regarding types of cancer and interventions, and included 5987 patients, 98.4% of whom had advancedstage disease (III and IV). There was no discernible effect on mortality with the use of LMWH (pooled OR 0.87, 95% CI 0.70-1.08; RR 0.94, 95% CI 0.86-1.04). Conclusions: In contrast to the previous study, these results did not show a survival benefit in cancer patients receiving LMWH. The effect of LMWH on overall survival in patients with limited-stage disease still is unknown.

Cisplatin induces the release of extracellular vesicles from ovarian cancer cells that can induce invasiveness and drug resistance in bystander cells

“…Another study revealed that heparin decreases cisplatin resistance of lung cancer cells (92). However other studies appear to suggest no benefit of adding heparin to conventional chemotherapy (93)(94)(95). The differences observed in these disparate studies may be down to subtle differences in methodology or the study model.…”

International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer

“…Overall, a signifi cant 45·0% reduction in VTE occurrence was reported across the six meta-analyses assessing the safety and effi cacy of LMWH compared with no intervention or placebo. [103][104][105][106]108,109 Specifi c cancer subgroup analyses across the meta-analyses showed that LMWH significantly reduced the VTE prevalence compared with no treatment or placebo by 67·9-71·2% in patients with pancreatic cancer (range of 430-748 patients) and by 50·3-53·6% in patients with lung cancer (range of 1926-2075 patients). 103,105 Five of six meta-analyses reported no signifi cant increase in major bleeding with LMWH (13·0-30·0% of patients received LMWH and had major bleeding) compared with no prophylaxis.…”

“…The updated search identifi ed eight meta-analyses (1669-9861 patients) [103][104][105][106][107][108][109][110] and six randomised clinical trials [111][112][113][114][115][116] comparing anticoagulant prophylaxis with no intervention or placebo in ambulatory patients receiving systemic anticancer therapy. Overall, a signifi cant 45·0% reduction in VTE occurrence was reported across the six meta-analyses assessing the safety and effi cacy of LMWH compared with no intervention or placebo.…”

Old and new applications of non-anticoagulant heparin

“…Other positive effects were observed in terminal cancer patients treated with Nadroparin or Dalteparin, as well as with Enoxaparin combined with chemotherapy in pancreatic cancer patients [29]. An updated systematic review and meta-analysis of randomized trials on survival of cancer patients treated with LMWHs has been reported [39]. A retrospective study on small cell lung cancer patients treated with heparin showed overall beneficial effects even when using different commercial heparin preparations [38].…”