Thromboprophylaxis in Patients Undergoing Orthopedic Surgeries; Focus on Cost-effective Analysis and Safety Comparison Between Rivaroxaban and Enoxaparin

There is a Today consensus that patients undergoing high-risk surgery should receive prophylaxis against postoperative venous thromboembolism (VTE). A good example of that could be orthopedic surgeries which place patients at unnecessary increased risk of fatal pulmonary embolism. For many years, pharmacotherapy options have been recommended by the American College of Chest Physicians (ACCP) for postoperative thromboprophylaxis were low-molecular-weight heparins (LMWHs), fondaparinux, and warfarin. However, their limitations have been repeatedly demonstrated in a huge number of randomized controlled trials (RCTs).

Since its introduction, low-molecular-weight heparins (LMWHs) are still common used in practice as thromboprophylactic agent. But, they require subcutaneous administration which making it challenging for use in settings other than the inpatient one. Despite the lower incidence of low-molecular-weight heparins (LMWHs) induced heparin-induced thrombocytopenia (HIT) compared with unfractionated heparins (UFH) in the postoperative setting, the risk of LMWH induced HIT in patients treated for VTE still concerns many clinicians. In addition to its subcutaneous administration, fondaparinux is contraindicated in severe renal impairment patients (with creatinine clearance (CrCl) <30 milliliter/minute) and those who have low body weight (<50 kg; venous thromboembolism prophylaxis only). While available orally, Vitamin K antagonists (VKAs) like Warfarin have unpredictable pharmacologic effects requiring a wakeful monitoring. Warfarin is also a remarkable source of food and drug interactions. As a result, it is mandatory to search for novel drugs or at least to search for new indications of really existing drugs.

In July 2011, the Food and Drug Administration (FDA) approved an orally administered selective factor Xa inhibitor called Rivaroxaban for the prevention of deep vein thrombosis (DVT) after total hip replacement (THR) or total knee replacement (TKR) surgeries. According to the Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism (RECORD) trials, rivaroxaban demonstrated superiority to enoxaparin in reducing venous thromboembolism without significant increase of bleeding risk. Rivaroxaban is recommended to be used at a fixed dose of 10 mg daily, with or without food, for 35 days following THR or 12 days following TKR.

Although the US Food and Drug Administration (FDA) advisory committee has recommended approval of rivaroxaban, many questions have been raised on the Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism (RECORD) trials of rivaroxaban. Some may argue that dosing was inconsistent with the recommendations. Others went far to say that the duration of treatment was inconsistent and did vary with enoxaparin. In other words, it was somewhat short.

Results from the ORTHO-TEP registry on joint replacement arthroplasty (hip and knee) from Dresden, Germany and Xarelto® in the Prophylaxis of Postsurgical Venous Thromboembolism after Elective Major Orthopaedic Surgery of the Hip or Knee (XAMOS) study are in accordance with the conclusion of Regulation of Coagulation in Major Orthopedic surgery reducing the Risk of DVT and PE (RECORD) trials. A subset of countries that participated in XAMOS also included patients undergoing fracture-related orthopedic surgery.