Background The first dose of rivaroxaban for venous thromboembolism (VTE) prophylaxis is recommended 6–10 h after major orthopaedic surgery; some patients may experience early postoperative nausea and vomiting, which may restrict the use of oral medications after surgery. Initiating thromboprophylaxis with subcutaneous low molecular weight heparin (LMWH) after surgery and transitioning to oral rivaroxaban may be an attractive option in this clinical situation.

Purpose To determine the pharmacodynamic effects of rivaroxaban after serial administration compared with responses on the first day of rivaroxaban after transitioning from postoperative LMWH.

Materials and methods An open-label, single-arm, multicentre study was conducted in the US, involving patients aged ≥18 years who had undergone elective unilateral total hip or total knee replacement and initially received LMWH thromboprophylaxis postoperatively. Thromboprophylaxis was planned for a minimum of 3 days and patients received the first dose of oral rivaroxaban (10 mg once daily) within 2 days of admission. The initial dose was given 22–28 h after the last dose of LMWH od, or 12–18 h after the last dose of LMWH twice daily. Blood samples were taken at baseline and at regular intervals on study days 1 and 3 for the measurement of antiFactor Xa activity and prothrombin time.

Results The safety population included 53 patients. Mean antiFactor Xa activity was not increased on day 1 versus day 3 but was slightly increased on day 3 compared with day 1 (p<0.01). There were no significant differences between the area under the concentration–time curves of antiFactor Xa activity on days 1 and 3. Mean prothrombin time was slightly, but not significantly, higher on day 1 than day 3 (p=0.11).

Conclusions These data support initiating oral rivaroxaban after a final dose of LMWH (od or twice daily) in patients who have undergone surgery and initially received LMWH prophylaxis.