Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy

Primary prophylaxis for venous thromboembolism (VTE) with LMWH reduces the incidence of symptomatic VTE and may reduce the incidence of symptomatic PE in ambulatory cancer patients receiving chemotherapy. It has no effect on 1-year total mortality but may increase the risk of major bleeding.

The recommendation is weak because of conflicting trials, potential bleeding, the need for laboratory monitoring and dose adjustment, and the relatively low incidence of VTE.

Summary

A Cochrane review included 26 studies with a total of 12 352 subjects to assess the efficacy and safety of primary thromboprophylaxis in ambulatory cancer patients receiving chemotherapy. All studies evaluated pharmacological interventions and performed mainly in people with locally advanced or metastatic cancer. The treatments evaluated consisted of LMWH (18 studies), the uLMWH semuloparin (1 study), UFH (1 study), the VKA warfarin (5 studies), antithrombin (1 study), and the oral direct factor Xa inhibitor apixaban (1 study).

The studies evaluating LMWH against placebo or no thromboprophylaxis varied in the duration and type of LMWH, including 8 weeks to 48 months of subcutaneous dalteparin, enoxaparin, certoparin, nadroparin, or bemiparin. The dose of LMWH was prophylactic in the majority of the studies. When compared with no thromboprophylaxis, LMWH significantly reduced the incidence of symptomatic VTE (table ) with a non-statistically significant 44% higher risk of major bleeding events. The reduction of symptomatic VTE corresponded to a NNTB of 30 (95% CI 23 to 56). In participants with multiple myeloma, LMWH was associated with a significant reduction in symptomatic VTE compared with the vitamin K antagonist warfarin (RR 0.33, 95% CI 0.14 to 0.83; 1 study, n=439), while the difference between LMWH and aspirin was not statistically significant (RR 0.51, 95% CI 0.22 to 1.17; 2 studies, n=781). Major bleeding was observed in none of the participants treated with LMWH or warfarin and in less than 1% of those treated with aspirin.

One large study (n=3 212) found a 64% (RR 0.36, 95% CI 0.22 to 0.60) reduction of symptomatic VTE with the ultra-low molecular weight heparin (uLMWH) semuloparin relative to placebo, with no apparent difference in major bleeding (RR 1.05, 95% CI 0.55 to 2.00). Only one study evaluated unfractionated heparin against no thromboprophylaxis but did not report on VTE or major bleeding. When compared with placebo, warfarin was associated with a non-statistically significant reduction of symptomatic VTE (RR 0.15, 95% CI 0.02 to 1.20; 1 study, n=311). Antithrombin, evaluated in one study involving paediatric patients, had no significant effect on VTE or on major bleeding when compared with no antithrombin. The direct oral factor Xa inhibitor apixaban was evaluated in a phase II dose-finding study that suggested a low rate of major bleeding (2.1% versus 3.4%) and symptomatic VTE (1.1% versus 13.8%) in comparison with placebo.

Clinical comment

Prophylaxis is suggested for hospitalized patients and patients with additional risk factors for VTE (patient, cancer or treatment-related) in absence of contraindications.

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Ədəbiyyat

1. Di Nisio M, Porreca E, Candeloro M et al. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev 2016;(12):CD008500. .