Relative effects of two different enoxaparin regimens as comparators against newer oral anticoagulants: Meta-analysis and adjusted indirect comparison

Background: Two different regimens of enoxaparin (40 mg once daily or 30 mg bid) have been used as control arms in trials of new oral anticoagulants. The choice of enoxaparin comparator may infl uence the perceived relative effi cacy and safety of the newer agents, and we aimed to identify any signifi cant differences between the two enoxaparin regimens. Methods: We searched MEDLINE, EMBASE, and Cochrane Library for randomized controlled trials that compared enoxaparin to oral anticoagulant (apixaban, dabigatran, rivaroxaban) thromboprophylaxis in elective total knee or hip arthroplasty. Total VTE and bleeding events were pooled using fi xed-effects meta-analysis and heterogeneity assessed with the I 2 statistic. We conducted adjusted indirect comparisons of bid vs once-daily enoxaparin regimes based on new oral anticoagulants as common comparators. Results: Fourteen randomized controlled trials in hip and knee replacement surgery met the inclusion criteria. Adjusted indirect comparison showed that bid enoxaparin was signifi cantly more effective in preventing VTE than enoxaparin once daily (relative risk [RR], 0.71; 95% CI, 0.61-0.83; P <.00001). For major and clinically relevant hemorrhage, adjusted indirect comparison showed that enoxaparin bid was nonsignifi cantly associated with increased risk of bleeding (RR 1.27; 95% CI, 0.97-1.65; P 5 .08) above that of enoxaparin once daily. Subgroup analysis limited to total knee arthroplasty trials showed similar results. Conclusions: The use of once-daily enoxaparin regimen as control in clinical trials will lead to more favorable estimates of relative effi cacy for the new oral anticoagulants than if enoxaparin 30 mg bid had been chosen as a comparator. © 2013 American College of Chest Physicians.