Economic Impact of Venous Thromboembolism After Hip and Knee Arthroplasty

Potential Impact of Rivaroxaban

Richard J Friedman; Nishan Sengupta; Michael Lees

Disclosures

Expert Rev Pharmacoeconomics Outcomes Res. 2011;11(3):299-306. 

In This Article

The RECORD Program

The Phase III clinical trial REgulation of Coagulation in ORthopaedic surgery to prevent Deep vein thrombosis and pulmonary embolism (RECORD) program consisted of four double-blind, randomized studies (two in THA and two in TKA), which compared the efficacy and safety of oral rivaroxaban with those of sc. enoxaparin – all trials used the same efficacy and safety outcomes.[43–46] Rivaroxaban is a novel oral, direct factor Xa inhibitor with a Ki for factor Xa of 0.4 nM.[47] It has a mean terminal half-life of 7–11 h.[48,49] Rivaroxaban does not directly affect platelet aggregation and it inhibits prothrombinase activity, as well as free and clot-associated factor Xa activity.[50,51] Rivaroxaban effectively inhibits thrombin generation by blocking the generation of activated factor X, thus preventing the conversion of prothrombin to thrombin.[52,53]

Patients undergoing THA received rivaroxaban 10 mg q.d. for 31–39 days or enoxaparin 40 mg q.d. (the regimen most commonly used in Europe) for 31–39 days (RECORD1)[43] or 10–14 days, followed by placebo (RECORD2).[44] In RECORD1, rivaroxaban reduced the incidence of the primary efficacy end point, total VTE (composite of symptomatic and asymptomatic DVT, nonfatal PE and all-cause mortality), which occurred in 1.1% of patients receiving rivaroxaban compared with 3.7% of patients receiving enoxaparin. Symptomatic VTE during treatment occurred in 0.3 and 0.5% of patients receiving rivaroxaban and enoxaparin, respectively. Major bleeding was low and not significantly different in both groups: 0.3 and 0.1%, respectively. Because of the unequal duration of thromboprophylaxis in RECORD2, which served to demonstrate the benefit of extended versus short-term prophylaxis, this trial was not used for the current analysis.

Patients undergoing TKA received rivaroxaban 10 mg q.d. or enoxaparin 40 mg q.d. (RECORD3)[45] or 30 mg twice daily (b.i.d., the dose commonly used in the USA) (RECORD4)[46] for 10–14 days. In RECORD3, rivaroxaban reduced the incidence of total VTE, which occurred in 9.6% of patients receiving rivaroxaban compared with 18.9% of patients receiving enoxaparin. Symptomatic VTE during treatment occurred in 0.7 and 2.0% of patients receiving rivaroxaban and enoxaparin, respectively. Major bleeding was low in both groups: 0.6 and 0.5%, respectively.[45] In RECORD4, rivaroxaban reduced the incidence of total VTE, which occurred in 6.9% of patients receiving rivaroxaban compared with 10.1% of patients receiving enoxaparin. Symptomatic VTE during treatment occurred in 0.7 and 1.2% of patients receiving rivaroxaban and enoxaparin, respectively. Major bleeding was low in both groups: 0.7 and 0.3%, respectively.

A pooled analysis of all four studies was recently performed to explore the impact of thromboprophylaxis with rivaroxaban on less-frequent clinical end points, the composite of symptomatic VTE and all-cause mortality, and safety outcomes that occurred at low frequency in the individual studies.[54] Rivaroxaban was found to reduce the primary composite end point, with a small but significant increase in the composite of major plus nonmajor clinically relevant bleeding events, and there were no signs of compromised liver safety and fewer serious adverse events compared with enoxaparin regimens.

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