JOA - 2026-06-12 - Journal Article
Risk and Benefit Profile with Concurrent Nonsteroidal Anti-Inflammatory Drugs and Direct Oral Anticoagulants Following Total Knee Arthroplasty.
Paul BR, Verhey JT, Haak GM, Braithwaite CL, Tarabichi S, Christopher ZK, Spangehl MJ, Bingham JS
Topics
Key Takeaway
Concurrent NSAID plus DOAC therapy after primary TKA increased surgical site infection risk (OR 1.71) and 2-year revision risk (OR 1.52) while reducing manipulation under anesthesia rates (OR 0.69) compared to DOAC alone.
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Summary
This study used a national claims database (2010–2023) to evaluate 90-day and 2-year outcomes in primary TKA patients on DOAC prophylaxis who were co-prescribed NSAIDs versus DOAC alone, using 1:3 propensity score matching. Combination therapy increased wound dehiscence (OR 1.49), surgical site infection (OR 1.71), PJI (OR 1.24), and 2-year revision (OR 1.52) without increasing 90-day bleeding events. Conversely, NSAID co-prescription reduced arthrofibrosis (OR 0.92) and manipulation under anesthesia (OR 0.69), with celecoxib and ibuprofen each carrying distinct wound and infection risk profiles.
Key Limitation
Claims-based design precludes verification of NSAID indication, dose, and actual patient adherence, meaning the infection and wound complication signal may reflect confounding by indication rather than a direct pharmacologic effect.
Original Abstract
BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed after total knee arthroplasty (TKA) for analgesia and inflammation control in conjunction with direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) prophylaxis in high-risk patients. In non-orthopaedic populations, concurrent NSAID-anticoagulant increases bleeding risk, but post-TKA safety data remain limited.
METHODS
Using a national claims database (2010 to 2023), we identified patients undergoing primary TKA who received DOAC-only VTE prophylaxis for ≥ three days. Patients co-prescribed NSAIDs were propensity score-matched 1:3 to DOAC-only patients based on demographics, comorbidities, and preoperative anticoagulant use. The matched cohort included 12,733 patients who received DOAC plus NSAID therapy and 37,127 who received DOAC alone. Outcomes included 90-day medical and surgical complications, two-year implant-related complications, and arthrofibrosis-associated outcomes. Subanalyses evaluated outcomes by NSAID type and prescription duration.
RESULTS
Combination therapy was associated with increased wound dehiscence (odds ratio (OR) 1.49, 95% confidence interval (CI) 1.20 to 1.87), surgical site infection (OR 1.71 [1.25 to 2.34]), and periprosthetic joint infection (OR 1.24 [1.01 to 1.52]), without differences in 90-day bleeding events (P > 0.05). At two years, NSAID plus DOAC therapy was associated with higher revision risk (OR 1.52 [1.13 to 2.05]), but lower arthrofibrosis (OR 0.92 [0.86 to 0.98]) and manipulation under-anesthesia rates (OR 0.69 [0.62 to 0.77]). Subgroup analyses demonstrated that celecoxib was associated with higher rates of wound dehiscence, surgical site infection, and blood loss anemia, while ibuprofen was associated with an increased risk of surgical site infection.
CONCLUSION
Patients who received concurrent NSAIDs with DOAC prophylaxis following TKA had higher rates of wound complications, infection, and all-cause revision, despite lower rates of arthrofibrosis-related outcomes. These findings demonstrate a clinically relevant trade-off and emphasize the importance of patient-specific risk stratification and cautious NSAID selection when used concurrently with DOAC therapy after TKA.