Apixaban vs. Enoxaparin for VTE Prevention After Hip Replacement

Introduction: VTE Risk After Hip Replacement

Hip replacement surgery puts its recipients at risk of deep venous thrombosis (DVT) or venous thromboembolism (VTE), whose complications include, but are not limited to, pulmonary embolism. With thousands of Americans opting for hip replacement every year, and statistics indicating that a significant percentage of patients develop thromboembolism after surgery, there is a need to formulate and adopt an effective preventive plan to minimize the risk of DVT or VTE after hip replacement surgery. This assertion is supported by Pannucci, Dreszer, Wachtman, Bailey, Portschy, Hamill, and Pusic (2011), who point out that the relevance of studies on the prevention of venous thromboembolism cannot be overstated, especially given that VTE is today regarded as an important post-operative patient safety concern.

Two of the most commonly used options in venous thromboembolism prevention are apixaban and enoxaparin. A review of how effective these two VTE and DVT mitigation mechanisms are, and how each compares to the other, is therefore not only relevant but also necessary. Apixaban works by inhibiting thrombus development — a consequence of thrombin formation — via the inhibition of active factor Xa. In essence, it is an anticoagulant. Treatment duration using apixaban is often dependent on the type of orthopedic surgery, which determines a patient's risk for venous thromboembolism. Enoxaparin, a type of heparin, is also an anticoagulant that helps activate antithrombin III, thereby effectively bringing about active factor Xa inhibition. Most studies cited herein made use of large samples, which are largely representative for generalization purposes and thus aid in the validity of findings.

Comparing Efficacy of Apixaban and Enoxaparin

In a study seeking to compare enoxaparin to apixaban on the effectiveness front, Lassen, Gallus, Raskob, Pineo, Chen, and Ramirez (2010) found that the latter was more effective in VTE prevention than the former. Lassen, Raskob, Gallus, Pineo, Chen, and Hornick (2010) also point out — albeit in the context of knee replacement surgery — that apixaban has a wider efficacy rate in comparison to enoxaparin. Knee replacement surgery has similarly been associated with the prevalence of deep vein thrombosis, which means that some parallels can be drawn between knee and hip replacement surgery. Lassen et al. (2010) indicate that, in comparison to enoxaparin, apixaban demonstrates a high rate of safety and efficiency in the prevention of venous thromboembolism after knee replacement surgery.

This is further corroborated by the findings of Nieto, Espada, Merino, and González (2012), who set out to determine how effective oral anticoagulants were in the treatment of VTE after either hip or knee replacement. The oral anticoagulants considered in this study included apixaban. The authors found that enoxaparin was less effective than apixaban in the treatment of VTE following either knee or hip surgery. However, unlike Lassen et al. (2010) — who found apixaban to be safer — Nieto et al. (2012) assigned the two interventions a similar safety score. It should be noted that no specific safety concern has been identified with regard to apixaban from previous clinical and nonclinical programs (Trkulja, 2016). The findings of Nieto et al. (2012) appear particularly applicable given the significant sample size used, in which a total of 32,144 patients were recruited. Furthermore, unlike Lassen et al. (2010), participants were drawn from various countries across the world, which is of great relevance for the generalizability of findings.

Like Lassen et al. (2010), Li, Sun, and Zhang (2012) rate apixaban as a more superior drug compared to enoxaparin in minimizing VTE occurrence following hip or knee surgery. However, unlike Lassen et al., most of the conclusions reached by Li et al. (2012) are based on a review of available data rather than original research. The mere assessment of previous studies could be viewed as a limitation, as it does not make meaningful additions to the existing body of research on this topic. Others who have found apixaban to be more effective in VTE prevention include Raskob, Gallus, Pineo, Chen, Ramirez, Wright, and Lassen (2012), who found that approximately 0.7% of apixaban patients suffered VTE, compared to approximately 1.5% of enoxaparin patients. Yan, Gu, Zhou, Lin, and Wu (2016) reached similar conclusions, asserting that enoxaparin does not compare favorably to apixaban and that the latter is associated with better outcomes. The only limitation of the Yan et al. (2016) study — unlike Raskob et al. (2012) — is that the generalizability of its findings may be restricted by its geographical scope, as the study was conducted entirely within China.

Notably, Raskob et al. (2012) left out an important variable — VTE-related mortality — which effectively limited the study's applicability in a practice setting. Yan et al. (2016), by contrast, went further by examining how the two regimens compared on the cost-effectiveness front. In a majority of cases, regimens with a higher efficacy rate tend to be more costly than those reporting lower rates of efficacy. This is upheld by Yan et al. (2016), who concluded that enoxaparin was more cost-effective than apixaban. It should, however, be noted that additional research is needed to support this cost-effectiveness claim, given that the study is largely limited to a specific geographical location and therefore lacks global applicability.

Post-Operative Bleeding and Dosage Considerations

Most studies seeking to measure major bleeding in the context of this issue have also found apixaban to be more effective than enoxaparin. According to Raskob et al. (2012), approximately 0.7% of apixaban patients experienced major bleeding, compared to 0.8% of enoxaparin patients. This finding is supported by Lassen et al. (2010), who also found that apixaban helped minimize bleeding. Both findings are consistent with the conclusions of Lassen et al. (2010), whose study reported 4% non-major bleeding for patients on apixaban, compared to 5% for those on enoxaparin. Unlike most studies cited herein, however, Lassen et al. (2010) do not make use of a double-blind, randomized controlled trial (RCT). For a study of this nature — in which comparisons between two regimens are drawn — an experimental design would have been more appropriate.

Enoxaparin has also fared poorly in studies gauging its effectiveness in the prevention of uncontrolled post-operative bleeding. Pannucci et al. (2011) found that enoxaparin had no meaningful impact on hematoma rates. Although that particular study does not concern itself specifically with VTE, its findings on enoxaparin's effectiveness in preventing uncontrolled bleeding confirm the findings of Raskob et al. (2012) and Lassen et al. (2010), who find apixaban more effective in preventing post-operative bleeding following hip replacement surgery. Lassen et al. (2010) additionally go further than other cited authors by defining the optimal dosage for maximum benefit, noting that 2.5 mg of apixaban is more effective in controlling post-operative bleeding following major joint surgery than 40 mg of enoxaparin. As Trkulja (2016) points out, the pharmacokinetic properties of apixaban are mostly favorable, particularly with regard to time and dose linearity, several pathways of elimination, and low intrasubject and intersubject variability.

Conclusion and Implications for Nursing Practice

Based on the synthesis above, apixaban appears to be safer as well as more effective than enoxaparin as a VTE regimen after hip replacement surgery. It should also be noted that, although this review was focused on VTE regimens following hip replacement surgery, its conclusions would be applicable to knee replacement surgery as well, in which case apixaban also appears to be not only safer but also more effective than enoxaparin. Furthermore, the findings of this synthesis suggest that apixaban may have fewer limitations in comparison to conventional thromboprophylactic agents, some of which relate to factors such as administration routes.

Enoxaparin, however, still remains applicable as an alternative to apixaban — particularly where concerns about cost arise, given that Yan et al. (2016) concluded that enoxaparin was more cost-effective than apixaban. Its effectiveness in preventing VTE among patients who undergo plastic surgery has also been upheld by Pannucci et al. (2011). Overall, the evidence reviewed here has direct applicability in clinical practice, and nurses and clinicians should consider both the efficacy and the cost profiles of these regimens when making individualized treatment decisions for patients undergoing major joint surgery.

References

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