Increased Risk of Stiffness following Total Knee Arthroplasty with Direct Oral Anticoagulants and Avoidance of Selective COX-2 Inhibitors

Abstract

Background Database studies demonstrate a strong association between use of direct oral anticoagulant (DOAC) medications and stiffness following total knee arthroplasty (TKA). The goal of this study was to evaluate whether the risk of stiffness in patients receiving a DOAC was affected by concomitant use or avoidance of a selective COX-2 inhibitor, when compared to a control group of patients receiving aspirin. Methods Consecutive primary TKA’s performed at a single institution between January 2014 - September 2019 were retrospectively reviewed. During this period, a risk-stratification algorithm for prophylaxis against venous thromboembolism (VTE) was used, with DOACs selected for patients at elevated VTE risk and aspirin for the remainder. Patients who required manipulation under anesthesia (MUA) within six months of index TKA were identified. Arc of motion (AOM) data at 6-weeks, 3-months, and 1-year was collected. Patients were divided into 3 groups based on postoperative medications prescribed: (a) Aspirin, (b) DOAC alone, and (c) DOAC + NSAID. Categorical variables were analyzed using Fisher’s Exact Tests and Pearson’s Chi-Square, while continuous variables were analyzed using Student’s T-test. Multivariate logistic regression was used to assess MUA risk while controlling for demographic differences. Results Forty patients underwent MUA from a population of 1,358 TKAs (2.9%). There was a significantly increased risk of MUA in patients where DOACs were used and concomitant NSAIDs were avoided when compared to the control group of patients receiving aspirin (5.4% vs 2.7%, OR 3.17; p = 0.029). This increased risk was not present when DOACs were used concomitantly with NSAIDs (3.1% vs 2.7%, OR 1.30; p = 0.573). In addition, less consistent AOM was achieved at 1-year postoperatively in the DOAC alone group compared to the control group of patients receiving aspirin (p=0.034). Conclusions Compared to aspirin anticoagulation, patients receiving DOACs without concomitant NSAIDs were more likely to develop postoperative stiffness requiring MUA and achieved less predictable AOM. The addition of selective COX-2 inhibitors may mitigate some risk of stiffness following primary TKA when anticoagulation with DOACs is necessary.