Elsevier

Thrombosis Research

Volume 126, Issue 3, September 2010, Pages 175-182
Thrombosis Research

Regular Article
Dabigatran versus enoxaparin for prevention of venous thromboembolism after hip or knee arthroplasty: A pooled analysis of three trials

https://doi.org/10.1016/j.thromres.2010.03.021Get rights and content

Abstract

Background

Three randomized, double-blind trials compared dabigatran, an oral direct thrombin inhibitor, with enoxaparin for the primary prevention of venous thromboembolism (VTE) in patients undergoing elective total hip and knee arthroplasty.

Objectives and Methods

We conducted a pre-specified pooled analysis of these trials. 8,210 patients were randomized, of whom 8,135 were treated (evaluable for safety) with dabigatran 220 mg or 150 mg once-daily, or subcutaneous enoxaparin (40 mg once-daily or 30 mg twice-daily). Efficacy analyses were based on the modified intention-to-treat population of 6,200 patients with an evaluable outcome. The common risk difference (RD) of treatment effect between each dabigatran dose and enoxaparin was estimated using fixed-effects models, and statistical heterogeneity was estimated using the I2 statistic.

Results

The composite outcome of major VTE (proximal deep vein thrombosis and/or pulmonary embolism) and VTE-related mortality occurred in 3.3% of the enoxaparin group versus 3.0% of the dabigatran 220 mg group (RD vs. enoxaparin -0.2%, 95% CI -1.3% to 0.9%, I2 = 37%) and 3.8% of the 150 mg group (RD vs. enoxaparin 0.5%, -0.6% to 1.6%, I2 = 0%). Major bleeding occurred in 1.4% of the enoxaparin group versus 1.4% of the dabigatran 220 mg group (RD vs. enoxaparin -0.2%, -0.8% to 0.5%, I2 = 40%) and 1.1% of the 150 mg group (RD vs. enoxaparin -0.4%, -1.0% to 0.2%, I2 = 0%).

Conclusions

Oral dabigatran was as effective as subcutaneous enoxaparin in reducing the risk of major VTE and VTE-related mortality after hip or knee arthroplasty and has a similar bleeding profile.

Section snippets

Data sources

RE-MOBILIZE, RE-MODEL and RE-NOVATE were prospective double-blind, double-dummy, randomized multicenter non-inferiority studies in adults aged at least 18 years who were scheduled for primary elective total hip or knee arthroplasty (Table 1). Patient characteristics were generally similar across the three trials, although in RE-MOBILIZE there was a higher proportion of non-Caucasian patients (4% black, 10% Asian and 12% Hispanic patients) (Table 2) [5], [6], [7].

The three trials had identical

Patients

Overall 8,210 patients were randomized between November 2004 and June 2006; 8,135 were treated (evaluable for safety), and 8,087 patients were operated and treated with oral dabigatran (n = 5,392) or subcutaneous enoxaparin (n = 2,695) (Supplementary Table 1). A further 1,887 (23.3%) patients were excluded from the mITT population mainly because bilateral venography was not performed (usually declined by the patient) or the venograms were considered indeterminate by the venography adjudication

Discussion

This pooled analysis of three major trials (RE-MOBILIZE, RE-MODEL, and RE-NOVATE) was designed to evaluate the effect of dabigatran on clinically relevant efficacy and safety outcomes. The findings show that dabigatran was as effective as enoxaparin in decreasing the risk of major VTE and VTE-related mortality. The common RD estimates were -0.2% (95% CI -1.3% to 0.9%) for 220 mg dabigatran and 0.5% (95% CI -0.6% to 1.6%) for 150 mg dabigatran. Although no non-inferiority margin was pre-specified,

Author Contributions

All authors (except Andreas Clemens) were members of the RE-MOBILIZE, RE-MODEL or RE-NOVATE steering committees. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE) and were fully responsible for all content and editorial decisions, and were involved at all stages of manuscript development.

Conflict of interest statement

Andreas Clemens, Stefan Hantel and Janet M Schnee are employees of Boehringer Ingelheim. All other authors received honoraria as members of the trial steering committees.

Acknowledgements

The authors thank the members of the data and safety monitoring board, the investigators, study coordinators and radiologists who participated in the trials, as listed in the original publications [5], [6], [7]. We thank Herbert Noack for assistance with the statistical analysis. All trials were sponsored by Boehringer Ingelheim (BI). This work was supported by BI. The authors received no compensation related to the development of the manuscript. Editorial assistance was provided, with funding

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