Venous thromboembolic (VTE) events are important causes of morbidity in elective total
hip replacement (THR) and total knee replacement (TKR) procedures. Current guidelines
recommend thromboprophylaxis in patients undergoing THR or TKR, although the American
Academy of Orthopaedic Surgeons (AAOS) guidelines suggest individual assessment of
patients when choosing the specific thromboprophylaxis strategy. Low molecular weight
heparin (LMWH) and adjusted-dose warfarin are the most commonly used anticoagulants for
thromboprophylaxis in the United States, but a number of other treatment options are available,
including unfractionated heparin, aspirin, mechanical devices, and newer oral anticoagulants.
Prior to 1980, rates of symptomatic VTE were 15 to 30 percent. However, improved surgical
care and techniques have decreased the rate of symptomatic VTE. A recent analysis that
incorporated data from trials and observational studies estimated the contemporary 35-day rate of
symptomatic VTE without thromboprophylaxis at 4.3 percent.
Pharmacological thromboprophylaxis for THR or TKR surgery decreases VTE by approximately
50 percent but with the tradeoff of increased bleeding. The risk of bleeding is a concern because
bleeding can lead to infections, reoperation, delayed wound healing, and extended hospital
stay. The choice of which antithrombotic thus becomes pivotal for balancing the prevention of
thromboembolism with the risk of bleeding. Newer oral anticoagulants have been developed
with the goal of overcoming the limitations of warfarin and the available parenteral agents.
These newer anticoagulants belong to two drug classes, based on their target coagulation protein:
factor Xa (FXa) inhibitors and direct thrombin inhibitors (DTIs). These drugs are given as fixed
oral doses and have the advantage of a more predictable anticoagulant effect, eliminating the
need for monitoring when used for short-term thromboprophylaxis. Disadvantages of newer
oral anticoagulants include the lack of specific antidotes to reverse their anticoagulant effect in a
timely fashion in case of bleeding, and drug costs.
Given the emerging data on new oral anticoagulants, this report was commissioned by the VA to
examine the following key questions (KQs):