Oral dabigatran etexilate versus enoxaparin for venous thromboembolism prevention after total hip arthroplasty

Pooled analysis of two phase 3 randomized trials

Bengt I. Eriksson, Ola E. Dahl, Nadia Rosencher, Andreas Clemens, Stefan Hantel, Martin Feuring, Jörg Kreuzer, Michael Huo, Richard J. Friedman

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Two phase 3 trials compared 28-35 days of treatment with oral dabigatran 220 mg or 150 mg (RE-NOVATE) or 220 mg (RE-NOVATE II) once daily with subcutaneous enoxaparin 40 mg once daily for prevention of venous thromboembolism (VTE) after elective total hip arthroplasty. Methods: This prespecified pooled analysis compared the outcomes for the dabigatran 220 mg dose with enoxaparin, which included 4,374 patients. Total VTE (venographic and symptomatic) plus all-cause mortality (primary efficacy), major VTE (proximal deep vein thrombosis [DVT] or non-fatal pulmonary embolism) plus VTE-related death, and bleeding events were evaluated. Efficacy analysis was based on the modified intention-to-treat (ITT) population and safety analysis was based on all treated patients. The common risk difference (RD) for dabigatran versus enoxaparin was estimated using a fixed effects model. Results: Total VTE and all-cause mortality occurred in 6.8 % (114/1,672) and 7.7 % (129/1,682) (RD:-0.8 %, 95 % confidence interval [CI] -2.6 to 0.9) for dabigatran and enoxaparin, respectively. Major VTE plus VTE-related mortality occurred in 2.7 % (46/1,714) and 4.0 % (69/1,711) (RD: -1.4 %, 95 % CI -2.6 to -0.2) of patients receiving dabigatran 220 mg and enoxaparin, respectively. Major bleeding occurred in 1.7 % (37/2,156) and 1.3 % (27/2,157) (RD: 0.5 %, 95 % CI -0.2 to 1.2), for dabigatran and enoxaparin respectively. Conclusions: Extended prophylaxis with oral dabigatran 220 mg once daily was as effective as enoxaparin 40 mg once daily in reducing the risk of total VTE and all-cause mortality after total hip arthroplasty, with a similar bleeding profile. The clinically relevant outcome of major VTE and VTE-related death was significantly reduced with dabigatran versus enoxaparin. Trial registration: NCT00657150and NCT00168818

Original languageEnglish (US)
Article number36
JournalThrombosis Journal
Volume13
Issue number1
DOIs
StatePublished - Nov 17 2015

Fingerprint

Enoxaparin
Venous Thromboembolism
Arthroplasty
Hip
Mortality
Confidence Intervals
Hemorrhage
Dabigatran
Pulmonary Embolism
Venous Thrombosis
Safety

Keywords

  • Arthroplasty
  • Bleeding
  • Dabigatran
  • Deep vein thrombosis
  • Enoxaparin
  • Mortality
  • Prophylaxis
  • Pulmonary embolism
  • Venous thromboembolism

ASJC Scopus subject areas

  • Hematology

Cite this

Oral dabigatran etexilate versus enoxaparin for venous thromboembolism prevention after total hip arthroplasty : Pooled analysis of two phase 3 randomized trials. / Eriksson, Bengt I.; Dahl, Ola E.; Rosencher, Nadia; Clemens, Andreas; Hantel, Stefan; Feuring, Martin; Kreuzer, Jörg; Huo, Michael; Friedman, Richard J.

In: Thrombosis Journal, Vol. 13, No. 1, 36, 17.11.2015.

Research output: Contribution to journalArticle

Eriksson, Bengt I. ; Dahl, Ola E. ; Rosencher, Nadia ; Clemens, Andreas ; Hantel, Stefan ; Feuring, Martin ; Kreuzer, Jörg ; Huo, Michael ; Friedman, Richard J. / Oral dabigatran etexilate versus enoxaparin for venous thromboembolism prevention after total hip arthroplasty : Pooled analysis of two phase 3 randomized trials. In: Thrombosis Journal. 2015 ; Vol. 13, No. 1.
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abstract = "Background: Two phase 3 trials compared 28-35 days of treatment with oral dabigatran 220 mg or 150 mg (RE-NOVATE) or 220 mg (RE-NOVATE II) once daily with subcutaneous enoxaparin 40 mg once daily for prevention of venous thromboembolism (VTE) after elective total hip arthroplasty. Methods: This prespecified pooled analysis compared the outcomes for the dabigatran 220 mg dose with enoxaparin, which included 4,374 patients. Total VTE (venographic and symptomatic) plus all-cause mortality (primary efficacy), major VTE (proximal deep vein thrombosis [DVT] or non-fatal pulmonary embolism) plus VTE-related death, and bleeding events were evaluated. Efficacy analysis was based on the modified intention-to-treat (ITT) population and safety analysis was based on all treated patients. The common risk difference (RD) for dabigatran versus enoxaparin was estimated using a fixed effects model. Results: Total VTE and all-cause mortality occurred in 6.8 {\%} (114/1,672) and 7.7 {\%} (129/1,682) (RD:-0.8 {\%}, 95 {\%} confidence interval [CI] -2.6 to 0.9) for dabigatran and enoxaparin, respectively. Major VTE plus VTE-related mortality occurred in 2.7 {\%} (46/1,714) and 4.0 {\%} (69/1,711) (RD: -1.4 {\%}, 95 {\%} CI -2.6 to -0.2) of patients receiving dabigatran 220 mg and enoxaparin, respectively. Major bleeding occurred in 1.7 {\%} (37/2,156) and 1.3 {\%} (27/2,157) (RD: 0.5 {\%}, 95 {\%} CI -0.2 to 1.2), for dabigatran and enoxaparin respectively. Conclusions: Extended prophylaxis with oral dabigatran 220 mg once daily was as effective as enoxaparin 40 mg once daily in reducing the risk of total VTE and all-cause mortality after total hip arthroplasty, with a similar bleeding profile. The clinically relevant outcome of major VTE and VTE-related death was significantly reduced with dabigatran versus enoxaparin. Trial registration: NCT00657150and NCT00168818",
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T1 - Oral dabigatran etexilate versus enoxaparin for venous thromboembolism prevention after total hip arthroplasty

T2 - Pooled analysis of two phase 3 randomized trials

AU - Eriksson, Bengt I.

AU - Dahl, Ola E.

AU - Rosencher, Nadia

AU - Clemens, Andreas

AU - Hantel, Stefan

AU - Feuring, Martin

AU - Kreuzer, Jörg

AU - Huo, Michael

AU - Friedman, Richard J.

PY - 2015/11/17

Y1 - 2015/11/17

N2 - Background: Two phase 3 trials compared 28-35 days of treatment with oral dabigatran 220 mg or 150 mg (RE-NOVATE) or 220 mg (RE-NOVATE II) once daily with subcutaneous enoxaparin 40 mg once daily for prevention of venous thromboembolism (VTE) after elective total hip arthroplasty. Methods: This prespecified pooled analysis compared the outcomes for the dabigatran 220 mg dose with enoxaparin, which included 4,374 patients. Total VTE (venographic and symptomatic) plus all-cause mortality (primary efficacy), major VTE (proximal deep vein thrombosis [DVT] or non-fatal pulmonary embolism) plus VTE-related death, and bleeding events were evaluated. Efficacy analysis was based on the modified intention-to-treat (ITT) population and safety analysis was based on all treated patients. The common risk difference (RD) for dabigatran versus enoxaparin was estimated using a fixed effects model. Results: Total VTE and all-cause mortality occurred in 6.8 % (114/1,672) and 7.7 % (129/1,682) (RD:-0.8 %, 95 % confidence interval [CI] -2.6 to 0.9) for dabigatran and enoxaparin, respectively. Major VTE plus VTE-related mortality occurred in 2.7 % (46/1,714) and 4.0 % (69/1,711) (RD: -1.4 %, 95 % CI -2.6 to -0.2) of patients receiving dabigatran 220 mg and enoxaparin, respectively. Major bleeding occurred in 1.7 % (37/2,156) and 1.3 % (27/2,157) (RD: 0.5 %, 95 % CI -0.2 to 1.2), for dabigatran and enoxaparin respectively. Conclusions: Extended prophylaxis with oral dabigatran 220 mg once daily was as effective as enoxaparin 40 mg once daily in reducing the risk of total VTE and all-cause mortality after total hip arthroplasty, with a similar bleeding profile. The clinically relevant outcome of major VTE and VTE-related death was significantly reduced with dabigatran versus enoxaparin. Trial registration: NCT00657150and NCT00168818

AB - Background: Two phase 3 trials compared 28-35 days of treatment with oral dabigatran 220 mg or 150 mg (RE-NOVATE) or 220 mg (RE-NOVATE II) once daily with subcutaneous enoxaparin 40 mg once daily for prevention of venous thromboembolism (VTE) after elective total hip arthroplasty. Methods: This prespecified pooled analysis compared the outcomes for the dabigatran 220 mg dose with enoxaparin, which included 4,374 patients. Total VTE (venographic and symptomatic) plus all-cause mortality (primary efficacy), major VTE (proximal deep vein thrombosis [DVT] or non-fatal pulmonary embolism) plus VTE-related death, and bleeding events were evaluated. Efficacy analysis was based on the modified intention-to-treat (ITT) population and safety analysis was based on all treated patients. The common risk difference (RD) for dabigatran versus enoxaparin was estimated using a fixed effects model. Results: Total VTE and all-cause mortality occurred in 6.8 % (114/1,672) and 7.7 % (129/1,682) (RD:-0.8 %, 95 % confidence interval [CI] -2.6 to 0.9) for dabigatran and enoxaparin, respectively. Major VTE plus VTE-related mortality occurred in 2.7 % (46/1,714) and 4.0 % (69/1,711) (RD: -1.4 %, 95 % CI -2.6 to -0.2) of patients receiving dabigatran 220 mg and enoxaparin, respectively. Major bleeding occurred in 1.7 % (37/2,156) and 1.3 % (27/2,157) (RD: 0.5 %, 95 % CI -0.2 to 1.2), for dabigatran and enoxaparin respectively. Conclusions: Extended prophylaxis with oral dabigatran 220 mg once daily was as effective as enoxaparin 40 mg once daily in reducing the risk of total VTE and all-cause mortality after total hip arthroplasty, with a similar bleeding profile. The clinically relevant outcome of major VTE and VTE-related death was significantly reduced with dabigatran versus enoxaparin. Trial registration: NCT00657150and NCT00168818

KW - Arthroplasty

KW - Bleeding

KW - Dabigatran

KW - Deep vein thrombosis

KW - Enoxaparin

KW - Mortality

KW - Prophylaxis

KW - Pulmonary embolism

KW - Venous thromboembolism

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JO - Thrombosis Journal

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