Low-molecular-weight heparin for venous thromboprophylaxis in ambulatory cancer patients: A meta-analysis

Abstract

9537 Background: Patients with cancer have an increased risk of venous thromboembolism (VTE). However, routine VTE prophylaxis is generally not recommended in ambulatory cancer patients. Several randomized controlled trials (RCTs) of low-molecular-weight heparin (LMWH) in ambulatory cancer patients have been reported with inconclusive results. Methods: A systematic review of RCTs of LMWH in ambulatory cancer patients without a VTE diagnosis was conducted. Included trials had to report VTE as primary or secondary outcome. An extensive electronic database search was conducted, including Medline, EMBASE, Cochrane Library along with abstracts from major meetings. Dual-blinded data extraction was performed. Meta-analysis was conducted using Mantel and Haenszel method to estimate relative risk (RR) and absolute risk difference (ARD) ± 95% CI. Primary outcomes in this analysis were all reported VTE and major bleeds. Most trials did not require VTE screening by imaging, precluding a separate analysis of asymptomatic VTE events. Results: Six RCTs were identified with a total of 2,648 patients including 1,525 receiving LMWH and 1,123 controls. No significant heterogeneity was observed across trials. Among patients receiving LMWH, the crude incidence of VTE was 2.95% compared to 5.25% among control patients. LMWH reduced the RR of VTE by 36% compared to controls (RR=0.64 [0.44 - 0.94], P=0.021), and reduced the ARD by 1.8% [0.2% - 3.4%]. Major bleeding events were reported in 1.57% LMWH patients compared to 0.98% in controls. The non-significant RR increase by LMWH for major bleeding was 1.85 [0.923 - 3.68], P=0.081, with an ARD of 0.9% [0.0% - 1.8%]. Results were comparable in the analysis limited to studies with VTE as primary outcome. Conclusions: While patients experienced a 36% relative risk reduction in VTE with LMWH, the absolute risk reduction was small, and concerns remain about the potential increase in major bleeding. Therefore, routine VTE prophylaxis in ambulatory cancer patients cannot be recommended at this time. Additional research is needed to identify cancer outpatients at high risk for VTE, in whom prophylaxis may have a more favorable risk-benefit ratio. [Table: see text]