Low-Molecular-Weight Heparin Outperforms Other Options for Inpatient VTE Prophylaxis

Most guidelines on preventing venous thromboembolism (VTE) in acutely ill medical patients recommend low-molecular-weight heparin (LMWH) or the pentasaccharide fondaparinux; some also recommend unfractionated heparin (UFH). However, guidelines often do not provide dose recommendations for heparins.

To evaluate pharmacologic VTE prophylaxis regimens and dosing, researchers conducted a meta-analysis of 44 trials (all conducted before the COVID-19 pandemic) in which 90,000 acutely ill medical inpatients were assigned as follows:

• LMWH (e.g., enoxaparin, low dose [<40 mg daily] or typical dose [40 mg daily or 30 mg twice daily])
• UFH (e.g., 5000 units twice daily or thrice daily)
• Prophylactic doses of direct-acting oral anticoagulants (DOACs; e.g., rivaroxaban [10 mg daily] or apixaban [2.5 mg twice daily])
• Prophylactic-dose fondaparinux (2.5 mg daily)
• Placebo or no intervention

Compared with placebo, typical prophylactic-dose LMWH and prophylactic-dose fondaparinux both significantly reduced symptomatic VTE (odds ratios, 0.66 and 0.32, respectively) — with LMWH results based on >20,000 patients (≈20 studies) and fondaparinux results based on <850 patients (single study). None of the interventions lowered mortality compared with placebo. Typical prophylactic-dose UFH (e.g., 5000 units thrice daily) and prophylactic-dose DOACs significantly increased major bleeding (ORs, 2.63 and 2.31, respectively).