Currently available anticoagulant therapies include warfarin, fondaparinux, and the more commonly used low molecular weight heparins, such as enoxaparin, bemiparin, and tinzaparin. These agents have demonstrated efficacy taurine 2-Aminoethanesulfonic acid but are associated with a number of limitations. There is a requirement for regular monitoring of warfarin and, in some regions, a requirement for the monitoring of platelet counts in those on LMWHs. Both LMWHs and fondaparinux require parenteral administration, and warfarin has a narrow therapeutic window which is difficult to attain.2 A number of new oral anticoagulants have been developed and are undergoing evaluation as thromboprophylaxis in orthopedic surgery. Rivaroxaban and dabigatran glycyrrhetin inhibitor etexilate have been assessed in large randomized controlled trials of THR and TKR surgery and have demonstrated similar or greater efficacy and similar safety compared with standard LMWH.5 10 Both rivaroxaban and dabigatran etexilate have been approved in over 70 countries for the prevention of VTE in patients having elective THR or TKR surgery.
Apixaban, recently approved in the European Union for the prevention of VTE following THR or TKR surgery, is a highly specific factor Xa inhibitor that is administered orally and does not require routine laboratory monitoring.12 Clinical trials in patients who have undergone elective THR and TKR have demonstrated that apixaban has improved efficacy, when compared with enoxaparin, in reducing VTE and all cause death, with a similar or lower risk of bleeding.13,14 The aim of this systematic review and meta analysis was to compare the efficacy and safety of berberine 633-65-8 apixaban versus other key comparators, for the prevention of VTE following elective TKR or THR surgery, via a series of direct and indirect comparisons and a network meta analysis.All the key outcomes of interest were measured using a dichotomous variable. The analyses were conducted on an intent to treat basis for the outcomes of bleeding. However, since asymptomatic DVT can only be detected via an evaluable venogram, the evaluable population was used in all analyses that included asymptomatic DVT. The ITT analyses for these outcomes were conducted as sensitivity analyses. Wherever a direct CC-5013 meta analysis was possible, this was conducted in Stata IC version 10.1 using the metan package SJ92: sbe243.19,20 Results were expressed as odds ratios and pooled using theDerSimonian and Laird random effects method, which takes account of between study variance.
The estimate of heterogeneity was via the Mantel Haenszel model. The indirect comparisons between apixaban and other treatments of interest via a common patient comparator were made using the Bucher method21 and the pooled ORs produced from the direct meta analysis. This method preserves randomization of treatments being compared indirectly.The NMA methods are built on the principles of indirect comparisons and are based on relative treatment effects in order to preserve trial randomization and minimize bias. A randomeffects NMA was conducted in WinBUGs version 1.4.1,22 24 which uses Bayesian Markov Chain Monte Carlo Gibbs sampling methods. Random effect models allow the true treatment effect to vary between studies due to heterogeneity. For the direct and indirect comparisons.