Aromatase conducted for rivaroxaban 10 mg once daily in the THR patient population, one including and one excluding the RECORD 2 study. RECORD 2 compared rivaroxaban 10 mg once daily with enoxaparin 40 mg once daily, however, enoxaparin was administered for only 10 to 14 days compared with 31 to 39 days of rivaroxaban. The shorter period of enoxaparin treatment, half that recommended in the National Institute of Health and Clinical Excellence VTE guideline,4 could lead to an overestimation of the treatment effect for rivaroxaban. Consequently, the 2 analyses were conducted in order to assess the variation in treatment effect clopidogrel contributed by this study.A total of 1809 publications were identified through electronic searches and a further 4 through handsearching andmanufacturer databases. Following assessment and exclusion of studies based on title, abstract, and full text, 40 records, reporting on 43 RCTs, were included in the final data set for the NMA.
Of the 43 studies identified in the final NMA data set, 25 did not compare the European licensed dose of the drug of interest with enoxaparin 40 mg once daily or enoxaparin 30 mg twice daily and were excluded from the direct/indirect meta analyses. Table 3 lists the studies identified by the systematic review, the interventions evaluated, and the outcomes evaluated in the TKR and THR patient populations. All the studies were included in the NMA, and highlighted VEGFR signaling pathway studies were included in the indirect comparison. The definition of major bleeding varied across studies. Twenty two studies reported a comparable majorbleeding outcome in the THR patient population and 16 studies in the TKR patient population. All other studies did not report a major bleeding outcome. There was a slight variation in the definition of CRNM bleeding across studies. Nine studies in the THR patient population and 11 in the TKR patient population high throughput screening reported a comparable CRNM bleeding outcome. Any bleeding was not reported as a distinct end point in all studies, therefore for these studies, the any bleeding end point used the reported major/minor/CRNM end points. If CRNM bleeding was reported as a distinct category of bleeding from minor bleeding, then major, minor, and CRNM bleeds were totaled, otherwise major and minor bleeds were totaled.
Data used in the meta analyses are available as an online supplement.In the absence of head to head RCT evidence for the new oral anticoagulants apixaban, rivaroxaban, and dabigatran, an adjusted indirect comparison with enoxaparin 40 mg once daily as the common comparator and an NMA were conducted to determine efficacy and safety effect sizes for these treatments. The patient adjusted indirect comparison found that in both the THR and TKR patient populations, apixaban was superior to dabigatran etexilate and similar to rivaroxaban for the prevention of the primary efficacy outcome all VTE and allcause death. Apixaban was similar to dabigatran and rivaroxaban for the prevention of major VTE, in both THR and TKR patient populations. The incidence of PE events was similar for apixaban, dabigatran etexilate, and rivaroxaban, however, the number of PEevents across all the treatments was small. The incidence of all bleeding events was comparable for apixaban, rivaroxaban, and dabigatran etexilate.