Is the Use of Apixaban or Enoxaparin, More Effective in the Prophylaxis of Venous Thromboembolism Post-Orthopedic Surgery?

OBJECTIVE: The objective of this selective EBM review is to determine whether or not the use of Apixaban or Enoxaparin is more effective in the prophylaxis of venous thromboembolism post-orthopedic surgery.

STUDY DESIGN : Review of three English language randomized, double-blind, placebo-controlled clinical trials from 2009-2010.

DATA SOURCES : Randomized, double-blind placebo controlled, clinical trials comparing the effectiveness of Apixaban and Enoxaparin in the prophylaxis of Venous Thromboembolism (VTE) post-orthopedic surgery were found using PubMed, the Cochrane Database of Randomized Controlled Trials, and the Cochrane Databases of Systematic Reviews.

OUTCOMES MEASURED: Development of venous thromboembolism (VTE) post-orthopedic surgery including Total Knee Replacement (TKR) and Total Hip Replacement (THR) compared to preoperative baseline was measured using four different modes of detection: Bilateral Venography, Ventilation Perfusion Scan, Spiral CT, Pulmonary Angiography, and bleeding during the treatment phase.

RESULTS: ADVANCE-1 (Apixaban Dose Orally vs. Anticoagulation with Enoxaparin) compared the efficacy of 2.5mg of Apixaban twice daily with that of Enoxaparin 30mg subcutaneous dosing twice daily post-TKR. Both regimens were initiated 12-24 hrs post surgery. No clear VTE rate reduction was evident with either drug, both exhibited similar results of 8.8% Enoxaparin, 9.0% Apixaban. However, reduced bleeding with Apixaban was observed. ADVANCE-2 focused on the two interventions, Apixaban 2.5mg twice daily initiated 12-24 hrs post surgery in comparison to Enoxaparin regimen of 40 mg subcutaneously 12 hrs prior and continued 10-14 days post-TKR. It was observed that Apixaban was superior to Enoxaparin post-TKR with a 9.3% relative reduction rate in VTE formation and 1% decline in bleeding episode. ADVANCE-3 evaluated the efficacy of Apixaban and Enoxaparin post-THR at the same dosage and administration as ADVANCE-2 TKR trial, however the treatment regimen was continued 35 days post-THR surgery. ADVANCE-3 trial concluded Apixaban was far more effective at VTE rate reduction with 1.4% compared with 3.9% of Enoxaparin use.

CONCLUSIONS :The use of Apixaban 2.5 mg orally twice daily is an appropriate, safe and effective
alternative to the traditional Enoxaparin for thromboprophylaxis post-orthopedic surgery.