The mainstay of venous thromboembolism (VTE) treatment is now the direct oral anticoagulants (DOACs), and the frontier is a new class designed to prevent clotting with even less bleeding.
Current standards, including cancer-associated VTE
For most VTE, DOACs have replaced warfarin. In cancer-associated VTE specifically, apixaban was non-inferior to the low-molecular-weight heparin dalteparin without a significant excess of major bleeding (the Caravaggio trial), and edoxaban was non-inferior to dalteparin for the composite of recurrent VTE or major bleeding, though with more major bleeding — chiefly gastrointestinal (Hokusai-VTE Cancer). DOACs are therefore first-line for many cancer patients, with LMWH still favored where gastrointestinal bleeding risk is high.
The factor XI frontier
The most active area of development is inhibition of factor XI/XIa, which aims to "decouple thrombosis from hemostasis" — blocking pathological clotting while largely sparing normal bleeding control. Several agents are in play: the oral inhibitors milvexian and asundexian, the antibody abelacimab, and antisense approaches. In VTE-prevention studies after knee arthroplasty, higher doses of abelacimab were superior to enoxaparin with very little bleeding, and milvexian showed similar promise. Phase 3 trials in cancer-associated VTE (abelacimab versus apixaban in ASTER, and versus dalteparin in MAGNOLIA) are underway, with abelacimab's once-monthly dosing and clearance independent of the liver and kidneys making it attractive for complex patients. An important nuance: factor XI inhibition is not uniformly successful — asundexian failed in atrial fibrillation — so its value appears indication-dependent, and the VTE data will determine its place. Other early antithrombotic targets include factor XII inhibitors, TAFI inhibitors (to enhance clot dissolution), and the glycoprotein VI inhibitor glenzocimab.
Further reading: Caravaggio apixaban (Agnelli et al., NEJM 2020); Hokusai-VTE Cancer edoxaban (Raskob et al., NEJM 2018); milvexian and abelacimab VTE-prevention trials (NEJM 2021); factor XI inhibitor reviews (Barnes, JTH 2025).