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Original Research: Antithrombotic Therapy |

Relative Effects of Two Different Enoxaparin Regimens as Comparators Against Newer Oral AnticoagulantsA Comparison of Two Different Enoxaparin Regimens: Meta-analysis and Adjusted Indirect Comparison

Chun Shing Kwok, MBBS; Shiva Pradhan, MBBS; Jessica Ka-yan Yeong, MBBS; Yoon K. Loke, MD
Author and Funding Information

From the Medical Division (Drs Kwok, Yeong, and Loke), Norfolk and Norwich University Hospitals National Health Service Foundation Trust; Population Health Group (Drs Kwok, Yeong, and Loke), Norwich Medical School, University of East Anglia; and Department of Medicine (Dr Pradhan), James Paget University Hospitals NHS Foundation Trust, Norfolk, England.

Correspondence to: Yoon K. Loke, MD, Norwich Medical School, University of East Anglia, Norwich, Norfolk, NR4 7TJ, England; e-mail: y.loke@uea.ac.uk


Funding/Support: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;144(2):593-600. doi:10.1378/chest.12-2634
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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 influence the perceived relative efficacy and safety of the newer agents, and we aimed to identify any significant 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 fixed-effects meta-analysis and heterogeneity assessed with the I2 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 significantly 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 nonsignificantly associated with increased risk of bleeding (RR 1.27; 95% CI, 0.97-1.65; P = .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 efficacy for the new oral anticoagulants than if enoxaparin 30 mg bid had been chosen as a comparator.

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