Retrospective Evaluation of Postoperative Adverse Drug Events in Patients Receiving Rivaroxaban After Major Orthopedic Surgery Compared with Standard Therapy in a Community Hospital.

STUDY OBJECTIVES: To evaluate the occurrence of bleeding and venous thromboembolic (VTE) events in patients receiving rivaroxaban, warfarin, or warfarin with the addition of enoxaparin during the immediate postoperative period following major orthopedic surgery.

METHODS: Patients older than 18 years who received at least one dose of rivaroxaban the morning following surgery, adjusted dose warfarin, or adjusted dose warfarin with the addition of enoxaparin for VTE prophylaxis after major orthopedic surgery between October 1, 2011, and February 28, 2015, were included. Data collected from the electronic health record included patient demographics, renal function, inpatient aspirin, P2Y12 inhibitor and/or nonsteroidal antiinflammatory drug (NSAID) use, type of surgery, postoperative analgesia, and presence of VTE risk factors. Adjusted incidence rate ratio for bleeding or VTE events was estimated using modified Poisson regression with robust standard errors. Covariates included in a multivariable model were age, sex, aspirin use, P2Y12 inhibitor use, NSAID use, obesity, VTE risk factors, and creatinine clearance.

RESULTS: There were 3246 patients who met study inclusion criteria. Overall, incidences of bleeding and VTE events were rare. Bleeding event incidence ranged from 0.4% in the warfarin and warfarin with the addition of enoxaparin groups to 1.2% in the rivaroxaban group (p=0.088). There were two major bleeding events and 18 minor bleeding events (including hemorrhagic wound complications). VTE event incidence ranged from 0.2% in the warfarin with the addition of enoxaparin group to 0.6% in the rivaroxaban group (p=0.230). Two deep vein thromboses and 10 pulmonary emboli occurred. With use of the multivariable model, the warfarin and warfarin with the addition of enoxaparin groups had significantly lower incidence rates of bleeding compared with rivaroxaban (incidence rate ratio [IRR] = 0.218, p=0.0120, and IRR = 0.242, p=0.021, respectively).

PRINCIPAL CONCLUSIONS: We observed a small, yet significant, increase in rivaroxaban-related bleeding in the immediate postoperative period relative to warfarin or warfarin with the addition of enoxaparin for the prevention of VTE after major orthopedic surgery.