Retrospective evaluation of postoperative adverse drug events in patients receiving rivaroxaban following major orthopedic surgery compared to standard therapy in a community hospital

tudy 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 post-operative 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 following 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 anti-inflammatory drug (NSAID) use, type of surgery, post-operative 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 3246 patients met study inclusion criteria. Overall, the incidence 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 eighteen 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 ten pulmonary emboli occurred. Using the multivariable model, the warfarin and warfarin with the addition of enoxaparin groups had significantly lower incidence rates of bleeding compared to rivaroxaban (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 prevention of VTE following major orthopedic surgery. This article is protected by copyright. All rights reserved.