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Thromb Haemost 2014; 112(03): 503-510
DOI: 10.1160/TH14-01-0064
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Indirect comparison meta-analysis of two enoxaparin regimens in patients undergoing major orthopaedic surgery

Impact on the interpretation of thromboprophylactic effects of new anticoagulant drugs
Silvy Laporte
1   EA3065, Université Jean Monnet, Saint-Etienne, France
2   Unité de Recherche Clinique, Innovation, Pharmacologie, Centre hospitalo-universitaire de Saint-Etienne, Hôpital Nord, Saint-Etienne, France
,
Céline Chapelle
2   Unité de Recherche Clinique, Innovation, Pharmacologie, Centre hospitalo-universitaire de Saint-Etienne, Hôpital Nord, Saint-Etienne, France
3   Inserm CIE3, Saint-Etienne, France
,
Laurent Bertoletti
1   EA3065, Université Jean Monnet, Saint-Etienne, France
4   Service de Médecine et Thérapeutique, Centre hospitalo-universitaire de Saint-Etienne, Hôpital Nord, Saint-Etienne, France
,
Jean-Christophe Lega
5   Service de Thérapeutique, Université Claude Bernard Lyon 1, Villeurbanne, France
6   Département de Médecine Interne et Pathologie Vasculaire, Hôpital Lyon Sud, Centre hospitalo-universitaire de Lyon, Pierre-Bénite, France
,
Michel Cucherat
7   UMR CNRS 5558 Evaluation et Modélisation des Effets Thérapeutiques, Université Claude Bernard Lyon 1, Villeurbanne, France
,
Paul J. Zufferey
1   EA3065, Université Jean Monnet, Saint-Etienne, France
2   Unité de Recherche Clinique, Innovation, Pharmacologie, Centre hospitalo-universitaire de Saint-Etienne, Hôpital Nord, Saint-Etienne, France
8   Service d’Anesthésie Réanimation, Centre hospitalo-universitaire de Saint-Etienne, Hôpital Nord, Saint-Etienne, France
,
Jean-Yves Darmon
9   Département Médical, MediBridge, Vélizy, France
,
Patrick Mismetti
1   EA3065, Université Jean Monnet, Saint-Etienne, France
2   Unité de Recherche Clinique, Innovation, Pharmacologie, Centre hospitalo-universitaire de Saint-Etienne, Hôpital Nord, Saint-Etienne, France
4   Service de Médecine et Thérapeutique, Centre hospitalo-universitaire de Saint-Etienne, Hôpital Nord, Saint-Etienne, France
,
the META-EMBOL Group › Author Affiliations Financial support: This work was part of the META-EMBOL project, supported by the Programme Hospitalier de Recherche Clinique 2008, Ministère de la Santé, France.
Further Information

Publication History

Received: 22 January 2014

Accepted after major revision: 08 January 2014

Publication Date:
02 December 2017 (online)

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Summary

Two enoxaparin dosage regimens are used as comparators to evaluate new anticoagulants for thromboprophylaxis in patients undergoing major orthopaedic surgery, but so far no satisfactory direct comparison between them has been published. Our objective was to compare the efficacy and safety of enoxaparin 3,000 anti-Xa IU twice daily and enoxaparin 4,000 anti-Xa IU once daily in this clinical setting by indirect comparison meta-analysis, using Bucher’s method. We selected randomised controlled trials comparing another anticoagulant, placebo (or no treatment) with either enoxaparin regimen for venous thromboembolism prophylaxis after hip or knee replacement or hip fracture surgery, provided that the second regimen was assessed elsewhere versus the same comparator. Two authors independently evaluated study eligibility, extracted the data, and assessed the risk of bias. The primary efficacy outcome was the incidence of venous thomboembolism. The main safety outcome was the incidence of major bleeding. Overall, 44 randomised comparisons in 56,423 patients were selected, 35 being double-blind (54,117 patients). Compared with enoxaparin 4,000 anti-Xa IU once daily, enoxaparin 3,000 anti-Xa IU twice daily was associated with a reduced risk of venous thromboembolism (relative risk [RR]: 0.53, 95% confidence interval [CI]: 0.40 to 0.69), but an increased risk of major bleeding (RR: 2.01, 95% CI: 1.23 to 3.29). In conclusion, when interpreting the benefit-risk ratio of new anticoagulant drugs versus enoxaparin for thromboprophylaxis after major orthopaedic surgery, the apparently greater efficacy but higher bleeding risk of the twice-daily 3,000 anti-Xa IU enoxaparin regimen compared to the once-daily 4,000 anti-Xa IU regimen should be taken into account.

Keywords

Heparin / LMWH - meta-analysis - oral anticoagulants - orthopaedics - venous thrombosis

* Members of the META-EMBOL Group are listed in the online supplementary material (available online at www.thrombosis-online.com).


 

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