Comparative Effectiveness and Safety of Anticoagulants in the Prevention of Venous Thromboembolism in Elective Hip and Knee Replacement Surgery Patients

One of the serious complications after an elective hip or knee replacement surgery is venous thromboembolism. Various anticoagulants are available for use as prophylactic agents after surgery in these patients. Rivaroxaban is one of the newer oral anticoagulant and offers multiple benefits over standard anticoagulation such as ease of administration, lack of monitoring and fewer food-drug interactions. However, the safety and effectiveness of rivaroxaban compared to warfarin in the real world is unknown. This study examined the association between patients newly initiating rivaroxaban compared to warfarin, treatment patterns, and the comparative effectiveness and safety in elective hip and knee replacement patients. A retrospective cohort of commercial and Medicare patients newly initiating rivaroxaban therapy or warfarin therapy after a hip or knee replacement surgery between January 1, 2011 and December 31, 2015 was identified. Patients who were new users, continuously enrolled for 6 months during the baseline period and three months after the surgery, greater than 18 years of age at the time of surgery, and had a procedure claim for total hip or knee replacement were included. Multivariate logistic regression was used to investigate the association between anticoagulant therapy and choice of anticoagulant. Logistic regression with inverse probability treatment weighing was used to examine the association between the choice of anticoagulant and VTE, bleeding and post-operative joint infection risk. Of the 117,393 commercially insured patients that were identified as undergoing elective total hip replacement surgery, 12,876 were new users of warfarin and 10,892 were new users of rivaroxaban. Of the 67,207 Medicare patients undergoing total hip replacement, 7,416 were new users of warfarin and 4,739 were new users of rivaroxaban. Among the 212,808 commercially insured patients undergoing knee replacement, 24,856 initiated warfarin and 21,398 initiated rivaroxaban. Of the 132,073 knee replacement patients in the Medicare cohort, 15,483 were new users of warfarin and 8,997 were new users of rivaroxaban. Among total hip replacement patients, warfarin users had significantly higher odds of deep vein thrombosis (OR 2.63, 95% CI 1.97-3.50 in commercial cohort and OR 1.78, 95% CI 1.38-2.29 in Medicare cohort) and pulmonary embolism (OR 2.60, 95% CI 2.04-3.31 in commercial cohort and OR 2.09, 95% CI 1.66-2.65 in Medicare cohort). The likelihood of deep vein thrombosis (OR 2.06, 95% CI 1.76-2.42 in commercial cohort and OR 2.21, 95% CI 1.84-2.65 in Medicare cohort) and pulmonary embolism (OR 2.03, 95% CI 1.78-2.33 in commercial cohort and OR 2.16, 95% CI 1.84-2.55 in Medicare cohort) was also higher in the warfarin users in the total knee replacement commercial and Medicare cohorts. There were no statistically significant differences in the bleeding risk among rivaroxaban new users and warfarin new users. The odds of postoperative joint infection (OR 1.57, 95% CI 1.16 -2.13 in commercial cohort and OR 1.79, 95% CI 1.14-2.81 in Medicare cohort) were significantly higher in the warfarin users compared to rivaroxaban users. The results from this dissertation suggest that treatment with rivaroxaban may help reduce the risk of incident VTE events without any significant increase in the risk of bleeding or post-operative joint infection compared to warfarin treatment in patients with a hip or knee replacement surgery.