Reducing the burden of venous thromboembolism in the acute medically ill population with extended-duration thromboprophylaxis

Hospitalized acute medically ill patients are vulnerable to venous thromboembolism (VTE), known as hospital-acquired thrombosis (HAT). The elevated risk of HAT is usually due to a combination of factors, with immobility and a prothrombotic state due to acute illness being the most frequent. The HAT risk persists well after hospital discharge, with more than half of events occurring after patient release. These HAT events may be fatal, and patients who survive the initial event may be subject to VTE recurrence, chronic discomfort from post-thrombotic syndrome and, although rare, may develop chronic thrombo-embolic pulmonary hypertension, which is often debilitating. The risk of HAT can be reduced with effective thromboprophylaxis. Current guidelines recommend thromboprophylaxis with subcutaneous heparin, low molecular weight heparin (LMWH) or fondaparinux for at-risk acute medically ill patients, but reports of real-world practice indicated that some patients do not receive protection in the short-term as outlined by the guidelines. Previous studies that have assessed extended thromboprophylaxis for 4-5 weeks with LMWH or direct oral anticoagulants in medically ill patients found they did not offer a net clinical benefit; any demonstrated efficacy was outweighed by the significantly increased risk of major haemorrhage. Therefore, there is an ongoing need for improved VTE prevention without increasing the risk of bleeding. In the APEX trial, conducted in an acute medically ill population, betrixaban provided a significant reduction in VTE events after 35 to 42 days of treatment compared with short-term enoxaparin without an increase in major bleeding.