CORR Insights®: Postoperative Thromboprophylaxis With New Oral Anticoagulants is Superior to LMWH in Hip Arthroplasty Surgery: Findings from the Swedish Registry

Where Are We Now? Dabigatran (Pradaxa®, Boehringer Ingelheim Pharmaceuticals, Ingelheim am Rhein, Germany), a direct thrombin inhibitor and new oral anticoagulant, was approved in the European Union in 2008 and by the FDA in 2010. Since then, factor Xa inhibitors including rivaroxaban, apixaban, and edoxaban have been approved and used for thromboprophylaxis. Several clinical trials demonstrated that these new oral anticoagulants are more effective than enoxaparin in reducing the risk of venous thromboembolism (VTE) after THA, with a similar safety profile [2-4]. In the current study, Kasina and colleagues [10] compared the efficacy and safety of new oral anticoagulants with low-molecular weight-heparins (LMWHs) based on the Swedish Hip Arthroplasty registry. The authors found that the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) were lower in the new oral anticoagulant group compared with the LMWH group, but that the two groups had no differences in the risk of bleeding, reoperation, and death. The current study confirmed the observations of previous clinical trials [2-4, 13] and showed, in my opinion, that new oral anticoagulants should replace LMWH for thromboprophylaxis after elective primary THA in patients who have risk factors for VTE. Where Do We Need To Go? Despite these results, there are still several gaps in our knowledge regarding new oral anticoagulants in patients undergoing THA. Various new oral anticoagulants are currently used, and most studies reported higher efficacy of these new anticoagulants compared with enoxaparin. However, each new oral anticoagulant has a different thromboprophylaxis efficacy and a different risk of bleeding. One study associated a higher efficacy among the new anticoagulants (including dabigatran, rivaroxaban, and apixaban) with a higher risk of bleeding [7]. Future studies will need to explore these differences in greater detail. Most metabolism of novel anticoagulants occurs in the liver, and excretion occurs both through the kidneys and via the feces. About one third of each dose is not metabolized at all, and is eliminated unchanged in the urine. Therefore, a reduction in renal function would decrease the renal clearance of new oral anticoagulants, and would affect its safety and tolerability [12]. Because of this, future studies need to evaluate the safe and effective dose of new oral anticoagulants in patients with compromised renal function. Aspirin and mechanical thromboprophylaxis with use of intermittent pneumatic compression have been reported as safe and effective thromboprophylaxis regimens after primary THA [8, 16]. However, to the best of my knowledge, no studies have compared new oral anticoagulants with aspirin or intermittent pneumatic compression and future studies need to do this. Finally, racial and ethnic differences exist in the risk of VTE after THA. East Asian patients may be less likely to develop symptomatic DVT and PE after that procedure [9, 11]. The utility of new oral anticoagulants therefore should be evaluated in a variety of patient populations around the world. How Do We Get There? Network meta-analysis is a methodology that allows the evaluation of multiple treatment modalities. It compares direct and indirect evidence on relative effectiveness of various treatments and provides a relative ranking of all treatments in terms of effectiveness with a reliable power [6], even when some of those interventions have not been compared directly with one another in randomized trials [1, 5]. Network meta-analysis might therefore be a good tool to compare the thromboprophylaxis effectiveness and bleeding risk of various new oral anticoagulants in patients undergoing THA. However, we do not currently have sufficient baseline data for the network meta-analysis. There is a paucity of head-to-head studies comparing various new oral anticoagulants in THA patients. Prospective randomized trials are not financially feasible. Moreover, each physician uses his or her preferred anticoagulant. Because of these limitations, a large scale multicenter study might be an alternative to compare the effectiveness of these new oral anticoagulants. In THA patients with impaired renal function, a dosage guideline of new oral anticoagulants according to the renal function is necessary. Creatinine clearance should be monitored in these new anticoagulant users, and dose-dependent effectiveness and safety should be determined. The patients should be stratified and evaluated according to creatinine clearance. A large scale randomized clinical trial could potentially answer whether new oral anticoagulants are superior to aspirin and/or intermittent pneumatic compression. A systematic review based on registry data is warranted in East Asia to determine the benefits and harms of new oral anticoagulants in patients from this part of the world, in light of their apparently diminished risk of thromboembolic complications [9]. Still, only a few registries in the region contain relevant information about thromboprophylaxis after THA. In South Korea, the Health Insurance Review and Assessment Service’s claims database [14], and the Korean Ministry of Health and Welfare’s Korean Hip Fracture registry [15] could be used for further investigations.