Patients with cancer-associated thrombosis (CAT) carry a higher risk of recurrence, bleeding and mortality as compared with non-cancer patients. The specific profiles of cancer patients, combining frequent co-morbidities, the use of anti-tumoral therapies and the cancer progression itself, represent a major therapeutic challenge for choosing a long-term anticoagulant treatment. This review discusses the practical basis of making a choice between the available drugs for a long-term antithrombotic strategy, linked to their pharmacology, mechanism of action, evidence of clinical benefits, and advantages and limitations in such a complex clinical context. In patients with cancer, low-molecular-weight heparins (LMWHs) are the preferred option for the secondary prevention of venous thromboembolism according to current guidelines, because their efficacy is significantly superior to vitamin K antagonists (VKAs). Even though LMWHs are effective and safe in cancer patients, they require daily subcutaneous injections, which may be problematic for a long-term therapy that may exceed 6 months' duration. Compared with VKAs, non-vitamin-K antagonist oral anticoagulants or direct oral anticoagulants (DOACs) are more target specific and do not require laboratory monitoring, whereas the oral route of administration makes them potentially attractive alternatives to LMWH. In randomized controlled trials in the general population DOACs have been shown to be non-inferior to VKAs in terms of efficacy with a lower rate of clinically relevant or major bleeding. However, given the limited number of cancer patients enrolled in these studies (with poorly defined active cancer), available trials are inconclusive regarding the usefulness of DOACs in the cancer setting. Ongoing head-to-head comparisons vs. LMWH in patients with CAT may allow an informed choice to be made regarding the DOAC option.
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