REMODEL study. A meta analysis of the three dabigatran studies supported the findings of RE MODEL and RE NOVATE. It showed that there were no significant differences between dabigatran 220 mg and enoxaparin in any endpoints when RE MODEL and RE NOVATE were analysed, or when all three trials were included in the analysis. Risk ratios for the composite of total VTE and allcause MK-2206 mortality were 0.95 in the twotrial analysis and 1.05 in the threetrial analysis.Major bleeding rates did not differ significantly when RE MODEL and RE NOVATE were analysed or when all three studies were analysed. In a recent prespecified pooled analysis of the studies, the primary outcome occurred in 3.3% of the enoxaparin group, 3.8% of the 150 mg group and 3.0% of the dabigatran 220 mg group. Rates of major bleeding were 1.
4% in the enoxaparin group, 1.1% in the 150 mg group and 1.4% in the dabigatran 220 mg group. These findings suggest that dabigatran was as effective as enoxaparin and the risk of major bleeding was similar. 2.3.3. Rivaroxaban. Rivaroxaban an oral, direct Roscovitine Factor Xa inhibitor was found to exhibit a predictable pharmacokinetic and pharmacodynamic profile and does not require dose adjustment for age, gender or weight. Rivaroxaban and its metabolites have a dual route of elimination: one third of the administered drug is cleared as unchanged active drug by the kidneys, one third is metabolized to inactive metabolites and then excreted by the kidneys, and one third is metabolized to inactive metabolites and then excreted by the faecal route.
Rivaroxaban has a low propensity for drug drug interactions with frequently used concomitant medications, such as naproxen, ASA or clopidogrel, and no interaction with the cardiac glycoside digoxin. Dietary restrictions are not necessary and rivaroxaban was given with or without food in the phase III VTE prevention studies. Phase II studies showed that all investigated rivaroxaban dose regimens had similar efficacy to enoxaparin, and the incidence of major bleeding was not significantly different to enoxaparin across a fourfold dose range. The RECORD programme comprised four phase III studies investigating the efficacy and safety of rivaroxaban in 12,500 patients undergoing THA and TKA. All 6 Thrombosis patients received rivaroxaban 10mg once daily 6 8 hours after surgery, and there was no upper age or weight limit for participation.
The primary efficacy endpoint was the composite of DVT, nonfatal PE and all cause mortality up to day 30 42 after surgery for RECORD1 and RECORD2, up to day 13 17 for RECORD3 and up to day 17 for RECORD4. The main safety endpoint was the incidence of treatment emergent major bleeding events. Other safety outcomes were also reported. RECORD1 showed that 5 weeks of extended duration rivaroxaban was significantly more effective than enoxaparin for extended duration prophylaxis in patients undergoing THA . Major bleeding events did not differ significantly between the groups. Clinically relevant nonmajor bleeding occurred in 2.9% of the rivaroxaban group versus 2.4% of the enoxaparin group, haemorrhagic wound complications in 1.5% versus 1.7% of patients, and postoperative wound infections in 0.4% of patients in both groups. The incidence of symptomatic VTE during treatment was not significantly different between the groups. RECORD2 demonstrated that extended duration rivaroxaban prophylaxis was significantly more effective than short duration prophylaxis with enoxaparin followed by p