Venous thromboembolism (VTE), which includes both deep vein thrombosis (DVT) and pulmonary embolism (PE), is the third leading cause of cardiovascular death in the United States with an approximate two million DVT cases and 600,000 PE cases annually.1 Patients undergoing total joint replacement are at high risk for VTE, where, in the absence of any prophylaxis, the incidence of venography-detected DVT ranges from 42% to 57% in total hip arthroplasty (THA) and 41% to 85% in total knee arthroplasty (TKA). The incidence of fatal PE without any prophylaxis ranges from 0.1% to 2% for THA and for 0.1% to 1.7% for TKA.2
Parenteral anticoagulants, such as low molecular weight heparin (LMWH), are the mainstay for the prophylaxis against VTE in patients who have undergone orthopedic surgery.3 However, their use has some limitations. For instance, patient education on administration is needed when used in the outpatient setting. Also, LMWHs are contraindicated in patients with severe renal insufficiency and in those with a history of heparin-induced thrombocytopenia.4
The recent American College of Chest Physicians (ACCP) antithrombotics guidelines offer new management options by introducing the new oral anticoagulants to the VTE prophylaxis of orthopedic patients. Whether these new agents are going to replace the old regimen is not clear yet, however, new evidence is giving us a new insight about what is the future of these agents.
A recent meta-analysis5 of 16 randomized clinical trials that included 38, 747 patients was done to compare the new oral anticoagulants (dabigatran, rivaroxaban and apixaban) with enoxaparin for prophylaxis against VTE after total hip or knee replacement. The main outcomes were both safety (bleeding) and efficacy (symptomatic VTE) by direct comparisons with enoxaparin and indirect comparisons between the new oral anticoagulants on the clinical outcomes of symptomatic VTE, bleeding, and death.
The authors found that, compared with enoxaparin, rivaroxaban was associated with a lower risk of VTE (relative risk 0.48, 95% confidence interval 0.31 to 0.75; P- value= 0.001), however, neither dabigatran (0.71, 0.23 to 2.12; P= 0.54) nor apixaban (0.82, 0.41 to 1.64; P= 0.57) reduced the risk of symptomatic VTE. Compared with enoxaparin, the relative risk of clinically relevant bleeding was higher with rivaroxaban (1.25, 95% CI 1.05 to 1.49; P= 0.01), similar with dabigatran (1.12, 0.94 to 1.35; P=0.21), and lower with apixaban (0.82, 0.69 to 0.98; P= 0.03). The treatments did not differ on the net clinical endpoint in direct or indirect comparisons. They concluded that the new anticoagulants did not differ significantly for efficacy and safety from that of enoxaparin; however, they may be associated with a higher bleeding tendency.
1. Jaffer A. An overview of venous thromboembolism: Impact, risks, and issues in prophylaxis. Cleveland clinic journal of medicine. 2008;75 (supl. 3):S3-S6.
2. Colwell CW. The ACCP guidelines for thrombophylaxis in total hip and knee arthroplasty. Orthopedics. 2009;32:67-71.
3. Falck-Ytter Y, Francis ...